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PDBsum entry 1xqh

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1xqh
Jmol
Contents
Protein chain
250 a.a. *
Ligands
LEU-LYS-SER-MLZ-
LYS-GLY
×2
SAH ×2
Waters ×717
* Residue conservation analysis
PDB id:
1xqh
Name: Transferase
Title: Crystal structure of a ternary complex of the methyltransferase set9 (also known as set7/9) with a p53 peptide and sah
Structure: Histone-lysine n-methyltransferase, h3 lysine-4 specific. Chain: a, e. Fragment: n-domain, set-domain. Synonym: lysine n-methyltransferase, histone h3-k4 methyltransferase, h3-k4-hmtase, set domain- containing set7, set9, set7/9. Engineered: yes. 9-mer peptide from tumor protein p53.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this sequence occurs naturally in humans.
Biol. unit: Tetramer (from PQS)
Resolution:
1.75Å     R-factor:   0.186     R-free:   0.223
Authors: S.Chuikov,J.K.Kurash,J.R.Wilson,B.Xiao,N.Justin,G.S.Ivanov, K.Mckinney,P.Tempst,C.Prives,S.J.Gamblin,N.A.Barlev, D.Reinberg
Key ref:
S.Chuikov et al. (2004). Regulation of p53 activity through lysine methylation. Nature, 432, 353-360. PubMed id: 15525938 DOI: 10.1038/nature03117
Date:
12-Oct-04     Release date:   23-Nov-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q8WTS6  (SETD7_HUMAN) -  Histone-lysine N-methyltransferase SETD7
Seq:
Struc:
366 a.a.
250 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.1.1.43  - Histone-lysine N-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N6-methyl-L-lysine-[histone]
S-adenosyl-L-methionine
+ L-lysine-[histone]
=
S-adenosyl-L-homocysteine
Bound ligand (Het Group name = SAH)
corresponds exactly
+ N(6)-methyl-L-lysine-[histone]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     chromosome   1 term 
  Biological process     regulation of transcription, DNA-dependent   2 terms 
  Biochemical function     histone-lysine N-methyltransferase activity     1 term  

 

 
    Added reference    
 
 
DOI no: 10.1038/nature03117 Nature 432:353-360 (2004)
PubMed id: 15525938  
 
 
Regulation of p53 activity through lysine methylation.
S.Chuikov, J.K.Kurash, J.R.Wilson, B.Xiao, N.Justin, G.S.Ivanov, K.McKinney, P.Tempst, C.Prives, S.J.Gamblin, N.A.Barlev, D.Reinberg.
 
  ABSTRACT  
 
p53 is a tumour suppressor that regulates the cellular response to genotoxic stresses. p53 is a short-lived protein and its activity is regulated mostly by stabilization via different post-translational modifications. Here we report a novel mechanism of p53 regulation through lysine methylation by Set9 methyltransferase. Set9 specifically methylates p53 at one residue within the carboxyl-terminus regulatory region. Methylated p53 is restricted to the nucleus and the modification positively affects its stability. Set9 regulates the expression of p53 target genes in a manner dependent on the p53-methylation site. The crystal structure of a ternary complex of Set9 with a p53 peptide and the cofactor product S-adenosyl-l-homocysteine (AdoHcy) provides the molecular basis for recognition of p53 by this lysine methyltransferase.
 
  Selected figure(s)  
 
Figure 1.
Figure 1: Set9 methylates p53 in vitro. a, Increasing amounts of GST -p53, GST -H3, histone octamers and recombinant histone nucleosomes were methylated by Set9, separated by 12% SDS -polyacrylamide gel electrophoresis (PAGE) transferred onto PVDF membrane, sprayed wit EN3HANCE and exposed to film (top). Coomassie-blue staining of the gel shown above (bottom). b, 3 g of core histones, p53, Gal4 -Vp16, cytochrome c, BSA or -globulin were tested as substrates for methylation by Set9, separated by 12% SDS -PAGE, and analysed by autoradiography. c, 3 g of recombinant histone octamers (recombinant nucleosomes for PR-Set7), full-length p53 and BSA were tested as substrates for methylation by Set9, Suv39H1, PR-Set7 or PRMT1 as indicated. d, Schematic representation of the C-terminal p53 peptides and lysine candidates for methylation (left). Methylation assay with the wild-type and mutant p53 peptides (right). e, Autoradiogram of methylation assay with full-length p53 WT and K372R mutant (top). Coomassie-blue staining of the methylation assay gel shown above (bottom). f, Schematic representation of the p53 domain structure and post-translational modifications at the C terminus. Circles, flags and the rectangle represent phosphorylation, acetylation and methylation of p53, respectively.
Figure 2.
Figure 2: Interaction of Set9 with p53 and H3 peptides. a, Alignment of protein sequences adjacent to lysines targeted for methylation in the case of histone H3 lysine 4, p53, TAF10, histone H3 lysine 9, histone H3 lysine 27, histone H3 lysine 36, and histone H4 lysine 20. Methylated lysine is highlighted in red and the asterisk represents the consensus for substrate recognition by Set9 methyltransferase. b, The dissociation constants of the p53 and H3 peptides, shown in inset, were determined using fluorometric competition assay. The unlabelled p53 and H3 peptides were used to displace a dansyl-labelled H3 10-mer of known affinity. The displacement curves were used to calculate the dissociation constants of the unlabelled peptides (shown in inset). c, Overall structure of the Set9 -p53 complex. Magenta, N-flanking domain; cyan, Set domain; blue, Set-I domain; beige, C-flanking domain. The backbone of the p53 peptide is green, and AdoHcy is yellow. d, Overlay of the peptide showing enzyme interactions for the Set9 -p53 complex and the Set9/H3 complex. The p53 carbon atoms are shown in green and H3 in grey. Hydrogen bonds are represented by dashed lines: only the Set9 donor/acceptor atoms are shown for each complex.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2004, 432, 353-360) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21276944 A.Dhayalan, S.Kudithipudi, P.Rathert, and A.Jeltsch (2011).
Specificity analysis-based identification of new methylation targets of the SET7/9 protein lysine methyltransferase.
  Chem Biol, 18, 111-120.  
  21141727 A.K.Upadhyay, and X.Cheng (2011).
Dynamics of histone lysine methylation: structures of methyl writers and erasers.
  Prog Drug Res, 67, 107-124.  
21328449 F.Shen, K.Z.Kirmani, Z.Xiao, B.H.Thirlby, R.J.Hickey, and L.H.Malkas (2011).
Nuclear protein isoforms: Implications for cancer diagnosis and therapy.
  J Cell Biochem, 112, 756-760.  
21071205 G.Schreiber, and A.E.Keating (2011).
Protein binding specificity versus promiscuity.
  Curr Opin Struct Biol, 21, 50-61.  
21151023 H.Parker, M.J.Rose-Zerilli, A.Parker, T.Chaplin, R.Wade, A.Gardiner, M.Griffiths, A.Collins, B.D.Young, D.G.Oscier, and J.C.Strefford (2011).
13q deletion anatomy and disease progression in patients with chronic lymphocytic leukemia.
  Leukemia, 25, 489-497.  
21436456 K.Zhang, T.Fischer, R.L.Porter, J.Dhakshnamoorthy, M.Zofall, M.Zhou, T.Veenstra, and S.I.Grewal (2011).
Clr4/Suv39 and RNA quality control factors cooperate to trigger RNAi and suppress antisense RNA.
  Science, 331, 1624-1627.  
21047797 L.Kaustov, H.Ouyang, M.Amaya, A.Lemak, N.Nady, S.Duan, G.A.Wasney, Z.Li, M.Vedadi, M.Schapira, J.Min, and C.H.Arrowsmith (2011).
Recognition and specificity determinants of the human cbx chromodomains.
  J Biol Chem, 286, 521-529.
PDB codes: 2l11 2l12 2l1b 3fdt 3gv6 3h91 3i90 3i91
21243721 O.Binda, M.Boyce, J.S.Rush, K.K.Palaniappan, C.R.Bertozzi, and O.Gozani (2011).
A chemical method for labeling lysine methyltransferase substrates.
  Chembiochem, 12, 330-334.  
21151116 P.O.Estève, Y.Chang, M.Samaranayake, A.K.Upadhyay, J.R.Horton, G.R.Feehery, X.Cheng, and S.Pradhan (2011).
A methylation and phosphorylation switch between an adjacent lysine and serine determines human DNMT1 stability.
  Nat Struct Mol Biol, 18, 42-48.
PDB code: 3os5
21243713 S.Krishnan, S.Horowitz, and R.C.Trievel (2011).
Structure and function of histone H3 lysine 9 methyltransferases and demethylases.
  Chembiochem, 12, 254-263.  
21119616 S.M.Carr, S.Munro, B.Kessler, U.Oppermann, and N.B.La Thangue (2011).
Interplay between lysine methylation and Cdk phosphorylation in growth control by the retinoblastoma protein.
  EMBO J, 30, 317-327.  
21088799 W.R.Liu, Y.S.Wang, and W.Wan (2011).
Synthesis of proteins with defined posttranslational modifications using the genetic noncanonical amino acid incorporation approach.
  Mol Biosyst, 7, 38-47.  
21245319 X.Liu, D.Wang, Y.Zhao, B.Tu, Z.Zheng, L.Wang, H.Wang, W.Gu, R.G.Roeder, and W.G.Zhu (2011).
Methyltransferase Set7/9 regulates p53 activity by interacting with Sirtuin 1 (SIRT1).
  Proc Natl Acad Sci U S A, 108, 1925-1930.  
21419134 Y.Chang, J.R.Horton, M.T.Bedford, X.Zhang, and X.Cheng (2011).
Structural insights for MPP8 chromodomain interaction with histone H3 lysine 9: potential effect of phosphorylation on methyl-lysine binding.
  J Mol Biol, 408, 807-814.
PDB code: 3qo2
20054697 A.Dettmann, Y.Jäschke, I.Triebel, J.Bogs, I.Schröder, and H.J.Schüller (2010).
Mediator subunits and histone methyltransferase Set2 contribute to Ino2-dependent transcriptional activation of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae.
  Mol Genet Genomics, 283, 211-221.  
20856808 B.D.Prasad, S.Goel, and P.Krishna (2010).
In silico identification of carboxylate clamp type tetratricopeptide repeat proteins in Arabidopsis and rice as putative co-chaperones of Hsp90/Hsp70.
  PLoS One, 5, e12761.  
20932800 C.Dai, and W.Gu (2010).
p53 post-translational modification: deregulated in tumorigenesis.
  Trends Mol Med, 16, 528-536.  
20137074 C.N.Pang, E.Gasteiger, and M.R.Wilkins (2010).
Identification of arginine- and lysine-methylation in the proteome of Saccharomyces cerevisiae and its functional implications.
  BMC Genomics, 11, 92.  
21037856 C.Oberle, and C.Blattner (2010).
Regulation of the DNA Damage Response to DSBs by Post-Translational Modifications.
  Curr Genomics, 11, 184-198.  
  20808952 C.V.Andreu-Vieyra, R.Chen, J.E.Agno, S.Glaser, K.Anastassiadis, A.F.Stewart, and M.M.Matzuk (2010).
MLL2 is required in oocytes for bulk histone 3 lysine 4 trimethylation and transcriptional silencing.
  PLoS Biol, 8, 0.  
21071677 C.Y.Park, S.A.Pierce, M.von Drehle, K.N.Ivey, J.A.Morgan, H.M.Blau, and D.Srivastava (2010).
skNAC, a Smyd1-interacting transcription factor, is involved in cardiac development and skeletal muscle growth and regeneration.
  Proc Natl Acad Sci U S A, 107, 20750-20755.  
20422671 D.Groff, P.R.Chen, F.B.Peters, and P.G.Schultz (2010).
A genetically encoded epsilon-N-methyl lysine in mammalian cells.
  Chembiochem, 11, 1066-1068.  
20703330 F.Pontvianne, T.Blevins, and C.S.Pikaard (2010).
Arabidopsis Histone Lysine Methyltransferases.
  Adv Bot Res, 53, 1.  
20603083 H.Kontaki, and I.Talianidis (2010).
Lysine methylation regulates E2F1-induced cell death.
  Mol Cell, 39, 152-160.  
19716451 H.Wei, and M.M.Zhou (2010).
Viral-encoded enzymes that target host chromatin functions.
  Biochim Biophys Acta, 1799, 296-301.  
21098664 J.Yang, J.Huang, M.Dasgupta, N.Sears, M.Miyagi, B.Wang, M.R.Chance, X.Chen, Y.Du, Y.Wang, L.An, Q.Wang, T.Lu, X.Zhang, Z.Wang, and G.R.Stark (2010).
Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes.
  Proc Natl Acad Sci U S A, 107, 21499-21504.  
  20370332 K.C.McKenna, and P.W.Chen (2010).
Influence of immune privilege on ocular tumor development.
  Ocul Immunol Inflamm, 18, 80-90.  
20714703 K.Nimura, K.Ura, and Y.Kaneda (2010).
Histone methyltransferases: regulation of transcription and contribution to human disease.
  J Mol Med, 88, 1213-1220.  
20588255 L.Chen, Z.Li, A.K.Zwolinska, M.A.Smith, B.Cross, J.Koomen, Z.M.Yuan, T.Jenuwein, J.C.Marine, K.L.Wright, and J.Chen (2010).
MDM2 recruitment of lysine methyltransferases regulates p53 transcriptional output.
  EMBO J, 29, 2538-2552.  
20657819 M.E.Pennini, S.Perrinet, A.Dautry-Varsat, and A.Subtil (2010).
Histone methylation by NUE, a novel nuclear effector of the intracellular pathogen Chlamydia trachomatis.
  PLoS Pathog, 6, e1000995.  
20121478 N.L.Young, M.D.Plazas-Mayorca, and B.A.Garcia (2010).
Systems-wide proteomic characterization of combinatorial post-translational modification patterns.
  Expert Rev Proteomics, 7, 79-92.  
20889125 R.Teperino, K.Schoonjans, and J.Auwerx (2010).
Histone methyl transferases and demethylases; can they link metabolism and transcription?
  Cell Metab, 12, 321-327.  
20140018 S.Munro, N.Khaire, A.Inche, S.Carr, and N.B.La Thangue (2010).
Lysine methylation regulates the pRb tumour suppressor protein.
  Oncogene, 29, 2357-2367.  
  20227666 S.Pagans, S.E.Kauder, K.Kaehlcke, N.Sakane, S.Schroeder, W.Dormeyer, R.C.Trievel, E.Verdin, M.Schnolzer, and M.Ott (2010).
The Cellular lysine methyltransferase Set7/9-KMT7 binds HIV-1 TAR RNA, monomethylates the viral transactivator Tat, and enhances HIV transcription.
  Cell Host Microbe, 7, 234-244.  
20307547 S.Roy, C.A.Musselman, I.Kachirskaia, R.Hayashi, K.C.Glass, J.C.Nix, O.Gozani, E.Appella, and T.G.Kutateladze (2010).
Structural insight into p53 recognition by the 53BP1 tandem Tudor domain.
  J Mol Biol, 398, 489-496.
PDB codes: 3lgf 3lgl 3lh0
21062871 T.Sahr, T.Adam, C.Fizames, C.Maurel, and V.Santoni (2010).
O-carboxyl- and N-methyltransferases active on plant aquaporins.
  Plant Cell Physiol, 51, 2092-2104.  
20160011 X.D.Yang, E.Tajkhorshid, and L.F.Chen (2010).
Functional interplay between acetylation and methylation of the RelA subunit of NF-kappaB.
  Mol Cell Biol, 30, 2170-2180.  
  20700496 Y.Pan, and R.Nussinov (2010).
Lysine120 interactions with p53 response elements can allosterically direct p53 organization.
  PLoS Comput Biol, 6, 0.  
19528079 A.Scoumanne, J.Zhang, and X.Chen (2009).
PRMT5 is required for cell-cycle progression and p53 tumor suppressor function.
  Nucleic Acids Res, 37, 4965-4976.  
18773966 A.Spannhoff, W.Sippl, and M.Jung (2009).
Cancer treatment of the future: inhibitors of histone methyltransferases.
  Int J Biochem Cell Biol, 41, 4.  
19864627 C.K.Ea, and D.Baltimore (2009).
Regulation of NF-kappaB activity through lysine monomethylation of p65.
  Proc Natl Acad Sci U S A, 106, 18972-18977.  
19381457 F.Lan, and Y.Shi (2009).
Epigenetic regulation: methylation of histone and non-histone proteins.
  Sci China C Life Sci, 52, 311-322.  
19334741 G.Cui, M.V.Botuyan, and G.Mer (2009).
Preparation of recombinant peptides with site- and degree-specific lysine (13)C-methylation.
  Biochemistry, 48, 3798-3800.  
19224996 H.Hannemann, K.Rosenke, J.M.O'Dowd, and E.A.Fortunato (2009).
The presence of p53 influences the expression of multiple human cytomegalovirus genes at early times postinfection.
  J Virol, 83, 4316-4325.  
19726520 H.Sivakumaran, A.van der Horst, A.J.Fulcher, A.Apolloni, M.H.Lin, D.A.Jans, and D.Harrich (2009).
Arginine methylation increases the stability of human immunodeficiency virus type 1 Tat.
  J Virol, 83, 11694-11703.  
19295133 I.R.Logan, H.V.McNeill, S.Cook, X.Lu, D.W.Meek, F.V.Fuller-Pace, J.Lunec, and C.N.Robson (2009).
Heat shock factor-1 modulates p53 activity in the transcriptional response to DNA damage.
  Nucleic Acids Res, 37, 2962-2973.  
19277210 J.Mullenders, A.W.Fabius, M.Madiredjo, R.Bernards, and R.L.Beijersbergen (2009).
A large scale shRNA barcode screen identifies the circadian clock component ARNTL as putative regulator of the p53 tumor suppressor pathway.
  PLoS ONE, 4, e4798.  
19098913 J.Wang, S.Hevi, J.K.Kurash, H.Lei, F.Gay, J.Bajko, H.Su, W.Sun, H.Chang, G.Xu, F.Gaudet, E.Li, and T.Chen (2009).
The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation.
  Nat Genet, 41, 125-129.  
19929178 K.A.Boehme, and C.Blattner (2009).
Regulation of p53--insights into a complex process.
  Crit Rev Biochem Mol Biol, 44, 367-392.  
19410540 K.H.Vousden, and C.Prives (2009).
Blinded by the Light: The Growing Complexity of p53.
  Cell, 137, 413-431.  
19216533 M.D.Huq, S.G.Ha, H.Barcelona, and L.N.Wei (2009).
Lysine methylation of nuclear co-repressor receptor interacting protein 140.
  J Proteome Res, 8, 1156-1167.  
19029252 M.J.MacPherson, L.G.Beatty, W.Zhou, M.Du, and P.D.Sadowski (2009).
The CTCF insulator protein is posttranslationally modified by SUMO.
  Mol Cell Biol, 29, 714-725.  
19734882 M.Mirouze, J.Reinders, E.Bucher, T.Nishimura, K.Schneeberger, S.Ossowski, J.Cao, D.Weigel, J.Paszkowski, and O.Mathieu (2009).
Selective epigenetic control of retrotransposition in Arabidopsis.
  Nature, 461, 427-430.  
19282482 P.O.Estève, H.G.Chin, J.Benner, G.R.Feehery, M.Samaranayake, G.A.Horwitz, S.E.Jacobsen, and S.Pradhan (2009).
Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells.
  Proc Natl Acad Sci U S A, 106, 5076-5081.  
19184981 P.V.Peña, C.A.Musselman, A.J.Kuo, O.Gozani, and T.G.Kutateladze (2009).
NMR assignments and histone specificity of the ING2 PHD finger.
  Magn Reson Chem, 47, 352-358.  
  19684477 S.Pradhan, H.G.Chin, P.O.Estève, and S.E.Jacobsen (2009).
SET7/9 mediated methylation of non-histone proteins in mammalian cells.
  Epigenetics, 4, 383-387.  
19208805 S.Raunser, R.Magnani, Z.Huang, R.L.Houtz, R.C.Trievel, P.A.Penczek, and T.Walz (2009).
Rubisco in complex with Rubisco large subunit methyltransferase.
  Proc Natl Acad Sci U S A, 106, 3160-3165.  
18923809 S.S.Ng, W.W.Yue, U.Oppermann, and R.J.Klose (2009).
Dynamic protein methylation in chromatin biology.
  Cell Mol Life Sci, 66, 407-422.  
19339993 S.Y.Wu, and C.M.Chiang (2009).
Crosstalk between sumoylation and acetylation regulates p53-dependent chromatin transcription and DNA binding.
  EMBO J, 28, 1246-1259.  
18984737 T.G.Deering, T.Ogihara, A.P.Trace, B.Maier, and R.G.Mirmira (2009).
Methyltransferase Set7/9 maintains transcription and euchromatin structure at islet-enriched genes.
  Diabetes, 58, 185-193.  
19434754 T.Gao, R.E.Collins, J.R.Horton, X.Zhang, R.Zhang, A.Dhayalan, R.Tamas, A.Jeltsch, and X.Cheng (2009).
The ankyrin repeat domain of Huntingtin interacting protein 14 contains a surface aromatic cage, a potential site for methyl-lysine binding.
  Proteins, 76, 772-777.
PDB code: 3eu9
19262565 X.D.Yang, B.Huang, M.Li, A.Lamb, N.L.Kelleher, and L.F.Chen (2009).
Negative regulation of NF-kappaB action by Set9-mediated lysine methylation of the RelA subunit.
  EMBO J, 28, 1055-1066.  
19219047 Y.Chang, X.Zhang, J.R.Horton, A.K.Upadhyay, A.Spannhoff, J.Liu, J.P.Snyder, M.T.Bedford, and X.Cheng (2009).
Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294.
  Nat Struct Mol Biol, 16, 312-317.
PDB code: 3fpd
  19736521 Y.Jacob, and S.D.Michaels (2009).
H3K27me1 is E(z) in animals, but not in plants.
  Epigenetics, 4, 366-369.  
  18581285 A.Scoumanne, and X.Chen (2008).
Protein methylation: a new mechanism of p53 tumor suppressor regulation.
  Histol Histopathol, 23, 1143-1149.  
18275858 B.Liu, Y.Chen, and D.K.St Clair (2008).
ROS and p53: a versatile partnership.
  Free Radic Biol Med, 44, 1529-1535.  
18092324 C.Heinlein, F.Krepulat, J.Löhler, D.Speidel, W.Deppert, and G.V.Tolstonog (2008).
Mutant p53(R270H) gain of function phenotype in a mouse model for oncogene-induced mammary carcinogenesis.
  Int J Cancer, 122, 1701-1709.  
18366598 C.J.Oldfield, J.Meng, J.Y.Yang, M.Q.Yang, V.N.Uversky, and A.K.Dunker (2008).
Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners.
  BMC Genomics, 9, S1.  
18221488 G.Brosch, P.Loidl, and S.Graessle (2008).
Histone modifications and chromatin dynamics: a focus on filamentous fungi.
  FEMS Microbiol Rev, 32, 409-439.  
18840612 I.Kachirskaia, X.Shi, H.Yamaguchi, K.Tanoue, H.Wen, E.W.Wang, E.Appella, and O.Gozani (2008).
Role for 53BP1 Tudor Domain Recognition of p53 Dimethylated at Lysine 382 in DNA Damage Signaling.
  J Biol Chem, 283, 34660-34666.  
19088188 J.F.Couture, L.M.Dirk, J.S.Brunzelle, R.L.Houtz, and R.C.Trievel (2008).
Structural origins for the product specificity of SET domain protein methyltransferases.
  Proc Natl Acad Sci U S A, 105, 20659-20664.
PDB codes: 3f9w 3f9x 3f9y 3f9z
18339539 J.Huang, and S.L.Berger (2008).
The emerging field of dynamic lysine methylation of non-histone proteins.
  Curr Opin Genet Dev, 18, 152-158.  
18280244 J.K.Kurash, H.Lei, Q.Shen, W.L.Marston, B.W.Granda, H.Fan, D.Wall, E.Li, and F.Gaudet (2008).
Methylation of p53 by Set7/9 mediates p53 acetylation and activity in vivo.
  Mol Cell, 29, 392-400.  
18471979 K.Subramanian, D.Jia, P.Kapoor-Vazirani, D.R.Powell, R.E.Collins, D.Sharma, J.Peng, X.Cheng, and P.M.Vertino (2008).
Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase.
  Mol Cell, 30, 336-347.
PDB codes: 3cbm 3cbo 3cbp
17891183 L.J.Warnock, R.Adamson, C.J.Lynch, and J.Milner (2008).
Crosstalk between site-specific modifications on p53 and histone H3.
  Oncogene, 27, 1639-1644.  
19043555 L.M.Johnson, J.A.Law, A.Khattar, I.R.Henderson, and S.E.Jacobsen (2008).
SRA-domain proteins required for DRM2-mediated de novo DNA methylation.
  PLoS Genet, 4, e1000280.  
18836468 M.Campoli, and S.Ferrone (2008).
HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance.
  Oncogene, 27, 5869-5885.  
17954561 M.Iizuka, O.F.Sarmento, T.Sekiya, H.Scrable, C.D.Allis, and M.M.Smith (2008).
Hbo1 Links p53-dependent stress signaling to DNA replication licensing.
  Mol Cell Biol, 28, 140-153.  
18195021 M.Sadaie, K.Shinmyozu, and J.Nakayama (2008).
A conserved SET domain methyltransferase, Set11, modifies ribosomal protein Rpl12 in fission yeast.
  J Biol Chem, 283, 7185-7195.  
18647749 O.Pless, E.Kowenz-Leutz, M.Knoblich, J.Lausen, M.Beyermann, M.J.Walsh, and A.Leutz (2008).
G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta.
  J Biol Chem, 283, 26357-26363.  
18505818 P.Li, H.Yao, Z.Zhang, M.Li, Y.Luo, P.R.Thompson, D.S.Gilmour, and Y.Wang (2008).
Regulation of p53 target gene expression by peptidylarginine deiminase 4.
  Mol Cell Biol, 28, 4745-4758.  
18488007 P.Trojer, and D.Reinberg (2008).
A gateway to study protein lysine methylation.
  Nat Chem Biol, 4, 332-334.  
18784729 R.J.Sims, and D.Reinberg (2008).
Is there a code embedded in proteins that is based on post-translational modifications?
  Nat Rev Mol Cell Biol, 9, 815-820.  
19003161 S.Kawamura, E.Yoshigai, S.Kuhara, and K.Tashiro (2008).
smyd1 and smyd2 are expressed in muscle tissue in Xenopus laevis.
  Cytotechnology, 57, 161-168.  
18247584 S.Y.Jung, Y.Li, Y.Wang, Y.Chen, Y.Zhao, and J.Qin (2008).
Complications in the assignment of 14 and 28 Da mass shift detected by mass spectrometry as in vivo methylation from endogenous proteins.
  Anal Chem, 80, 1721-1729.  
19022177 T.J.Kang, S.Yuzawa, and H.Suga (2008).
Expression of histone H3 tails with combinatorial lysine modifications under the reprogrammed genetic code for the investigation on epigenetic markers.
  Chem Biol, 15, 1166-1174.  
18431400 T.Riley, E.Sontag, P.Chen, and A.Levine (2008).
Transcriptional control of human p53-regulated genes.
  Nat Rev Mol Cell Biol, 9, 402-412.  
18483220 T.Terzian, Y.A.Suh, T.Iwakuma, S.M.Post, M.Neumann, G.A.Lang, C.S.Van Pelt, and G.Lozano (2008).
The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss.
  Genes Dev, 22, 1337-1344.  
18573881 W.W.Tsai, T.T.Nguyen, Y.Shi, and M.C.Barton (2008).
p53-targeted LSD1 functions in repression of chromatin structure and transcription in vivo.
  Mol Cell Biol, 28, 5139-5146.  
18697203 W.Yang, D.Wetterskog, Y.Matsumoto, and K.Funa (2008).
Kinetics of repression by modified p53 on the PDGF beta-receptor promoter.
  Int J Cancer, 123, 2020-2030.  
18722172 X.J.Yang, and E.Seto (2008).
Lysine acetylation: codified crosstalk with other posttranslational modifications.
  Mol Cell, 31, 449-461.  
19074285 Y.Chinenov, M.A.Sacta, A.R.Cruz, and I.Rogatsky (2008).
GRIP1-associated SET-domain methyltransferase in glucocorticoid receptor target gene expression.
  Proc Natl Acad Sci U S A, 105, 20185-20190.  
18650421 Y.Li, M.A.Reddy, F.Miao, N.Shanmugam, J.K.Yee, D.Hawkins, B.Ren, and R.Natarajan (2008).
Role of the histone H3 lysine 4 methyltransferase, SET7/9, in the regulation of NF-kappaB-dependent inflammatory genes. Relevance to diabetes and inflammation.
  J Biol Chem, 283, 26771-26781.  
17627286 A.Olsson, C.Manzl, A.Strasser, and A.Villunger (2007).
How important are post-translational modifications in p53 for selectivity in target-gene transcription and tumour suppression?
  Cell Death Differ, 14, 1561-1575.  
17301803 A.Ozer, and R.K.Bruick (2007).
Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one?
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17409384 A.Scoumanne, and X.Chen (2007).
The lysine-specific demethylase 1 is required for cell proliferation in both p53-dependent and -independent manners.
  J Biol Chem, 282, 15471-15475.  
17707224 C.H.Henkels, and S.Khorasanizadeh (2007).
Implications of a histone code mimic in epigenetic signaling.
  Mol Cell, 27, 521-522.  
17512990 D.W.Ng, T.Wang, M.B.Chandrasekharan, R.Aramayo, S.Kertbundit, and T.C.Hall (2007).
Plant SET domain-containing proteins: structure, function and regulation.
  Biochim Biophys Acta, 1769, 316-329.  
17923682 G.D.Gregory, C.R.Vakoc, T.Rozovskaia, X.Zheng, S.Patel, T.Nakamura, E.Canaani, and G.A.Blobel (2007).
Mammalian ASH1L is a histone methyltransferase that occupies the transcribed region of active genes.
  Mol Cell Biol, 27, 8466-8479.  
17646389 G.S.Ivanov, T.Ivanova, J.Kurash, A.Ivanov, S.Chuikov, F.Gizatullin, E.M.Herrera-Medina, F.Rauscher, D.Reinberg, and N.A.Barlev (2007).
Methylation-acetylation interplay activates p53 in response to DNA damage.
  Mol Cell Biol, 27, 6756-6769.  
17517655 H.B.Guo, and H.Guo (2007).
Mechanism of histone methylation catalyzed by protein lysine methyltransferase SET7/9 and origin of product specificity.
  Proc Natl Acad Sci U S A, 104, 8797-8802.  
17962312 H.G.Chin, P.O.Estève, M.Pradhan, J.Benner, D.Patnaik, M.F.Carey, and S.Pradhan (2007).
Automethylation of G9a and its implication in wider substrate specificity and HP1 binding.
  Nucleic Acids Res, 35, 7313-7323.  
17984964 J.A.Latham, and S.Y.Dent (2007).
Cross-regulation of histone modifications.
  Nat Struct Mol Biol, 14, 1017-1024.  
17805299 J.Huang, R.Sengupta, A.B.Espejo, M.G.Lee, J.A.Dorsey, M.Richter, S.Opravil, R.Shiekhattar, M.T.Bedford, T.Jenuwein, and S.L.Berger (2007).
p53 is regulated by the lysine demethylase LSD1.
  Nature, 449, 105-108.  
17785449 K.Batta, and T.K.Kundu (2007).
Activation of p53 function by human transcriptional coactivator PC4: role of protein-protein interaction, DNA bending, and posttranslational modifications.
  Mol Cell Biol, 27, 7603-7614.  
17804642 K.J.Riley, and L.J.Maher (2007).
p53 RNA interactions: new clues in an old mystery.
  RNA, 13, 1825-1833.  
17068503 L.M.Rozan, and W.S.El-Deiry (2007).
p53 downstream target genes and tumor suppression: a classical view in evolution.
  Cell Death Differ, 14, 3-9.  
17210650 M.A.Jedrusik, and E.Schulze (2007).
Linker histone HIS-24 (H1.1) cytoplasmic retention promotes germ line development and influences histone H3 methylation in Caenorhabditis elegans.
  Mol Cell Biol, 27, 2229-2239.  
17898864 M.K.Lee, and K.Sabapathy (2007).
Phosphorylation at carboxyl-terminal S373 and S375 residues and 14-3-3 binding are not required for mouse p53 function.
  Neoplasia, 9, 690-698.  
17442611 M.Lohrum, H.G.Stunnenberg, and C.Logie (2007).
The new frontier in cancer research: deciphering cancer epigenetics.
  Int J Biochem Cell Biol, 39, 1450-1461.  
17158927 M.Mattia, V.Gottifredi, K.McKinney, and C.Prives (2007).
p53-Dependent p21 mRNA elongation is impaired when DNA replication is stalled.
  Mol Cell Biol, 27, 1309-1320.  
17635932 R.Magnani, N.R.Nayak, M.Mazarei, L.M.Dirk, and R.L.Houtz (2007).
Polypeptide substrate specificity of PsLSMT. A set domain protein methyltransferase.
  J Biol Chem, 282, 27857-27864.  
17707231 S.C.Sampath, I.Marazzi, K.L.Yap, S.C.Sampath, A.N.Krutchinsky, I.Mecklenbräuker, A.Viale, E.Rudensky, M.M.Zhou, B.T.Chait, and A.Tarakhovsky (2007).
Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly.
  Mol Cell, 27, 596-608.  
17694091 S.Mujtaba, L.Zeng, and M.M.Zhou (2007).
Structure and acetyl-lysine recognition of the bromodomain.
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17388541 S.Wang, P.Hu, and Y.Zhang (2007).
Ab initio quantum mechanical/molecular mechanical molecular dynamics simulation of enzyme catalysis: the case of histone lysine methyltransferase SET7/9.
  J Phys Chem B, 111, 3758-3764.  
17401426 T.Iwakuma, and G.Lozano (2007).
Crippling p53 activities via knock-in mutations in mouse models.
  Oncogene, 26, 2177-2184.  
17719542 T.Tanaka, S.Ohkubo, I.Tatsuno, and C.Prives (2007).
hCAS/CSE1L associates with chromatin and regulates expression of select p53 target genes.
  Cell, 130, 638-650.  
17374386 X.Cheng, and X.Zhang (2007).
Structural dynamics of protein lysine methylation and demethylation.
  Mutat Res, 618, 102-115.  
17545996 X.J.Yang, and S.Grégoire (2007).
Metabolism, cytoskeleton and cellular signalling in the grip of protein Nepsilon - and O-acetylation.
  EMBO Rep, 8, 556-562.  
17707234 X.Shi, I.Kachirskaia, H.Yamaguchi, L.E.West, H.Wen, E.W.Wang, S.Dutta, E.Appella, and O.Gozani (2007).
Modulation of p53 function by SET8-mediated methylation at lysine 382.
  Mol Cell, 27, 636-646.  
17173055 Y.B.Schwartz, and V.Pirrotta (2007).
Polycomb silencing mechanisms and the management of genomic programmes.
  Nat Rev Genet, 8, 9.  
16497245 A.Maeda, S.Nakamura, M.Isono, M.Osaki, H.Ito, and K.Sato (2006).
Induction of efficient apoptosis and cell-cycle arrest in tumor cells by adenovirus-mediated p53 A4 mutant.
  Pathol Int, 56, 126-134.  
16946699 A.Schuetz, A.Allali-Hassani, F.Martín, P.Loppnau, M.Vedadi, A.Bochkarev, A.N.Plotnikov, C.H.Arrowsmith, and J.Min (2006).
Structural basis for molecular recognition and presentation of histone H3 by WDR5.
  EMBO J, 25, 4245-4252.
PDB codes: 2gnq 2h9l 2h9m 2h9n 2h9o 2h9p 2o9k
16648462 A.Vaquero, M.B.Scher, D.H.Lee, A.Sutton, H.L.Cheng, F.W.Alt, L.Serrano, R.Sternglanz, and D.Reinberg (2006).
SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis.
  Genes Dev, 20, 1256-1261.  
16943427 C.Chao, Z.Wu, S.J.Mazur, H.Borges, M.Rossi, T.Lin, J.Y.Wang, C.W.Anderson, E.Appella, and Y.Xu (2006).
Acetylation of mouse p53 at lysine 317 negatively regulates p53 apoptotic activities after DNA damage.
  Mol Cell Biol, 26, 6859-6869.  
16441846 C.Kamel, M.Abrol, K.Jardine, X.He, and M.W.McBurney (2006).
SirT1 fails to affect p53-mediated biological functions.
  Aging Cell, 5, 81-88.  
16455486 C.L.Brooks, and W.Gu (2006).
p53 ubiquitination: Mdm2 and beyond.
  Mol Cell, 21, 307-315.  
16888766 D.J.Hoelz, R.J.Arnold, L.E.Dobrolecki, W.Abdel-Aziz, A.P.Loehrer, M.V.Novotny, L.Schnaper, R.J.Hickey, and L.H.Malkas (2006).
The discovery of labile methyl esters on proliferating cell nuclear antigen by MS/MS.
  Proteomics, 6, 4808-4816.  
17128209 F.Toledo, and G.M.Wahl (2006).
Regulating the p53 pathway: in vitro hypotheses, in vivo veritas.
  Nat Rev Cancer, 6, 909-923.  
16288459 G.Liu, and X.Chen (2006).
Regulation of the p53 transcriptional activity.
  J Cell Biochem, 97, 448-458.  
16575406 G.M.Wahl (2006).
Mouse bites dogma: how mouse models are changing our views of how P53 is regulated in vivo.
  Cell Death Differ, 13, 973-983.  
16845004 H.Chen, Y.Xue, N.Huang, X.Yao, and Z.Sun (2006).
MeMo: a web tool for prediction of protein methylation modifications.
  Nucleic Acids Res, 34, W249-W253.  
16464568 I.H.Su, and A.Tarakhovsky (2006).
Lysine methylation and 'signaling memory'.
  Curr Opin Immunol, 18, 152-157.  
16415881 J.F.Couture, E.Collazo, G.Hauk, and R.C.Trievel (2006).
Structural basis for the methylation site specificity of SET7/9.
  Nat Struct Mol Biol, 13, 140-146.
PDB code: 2f69
16682405 J.F.Couture, G.Hauk, M.J.Thompson, G.M.Blackburn, and R.C.Trievel (2006).
Catalytic roles for carbon-oxygen hydrogen bonding in SET domain lysine methyltransferases.
  J Biol Chem, 281, 19280-19287.
PDB codes: 2h21 2h23 2h2e 2h2j
17070031 J.F.Couture, and R.C.Trievel (2006).
Histone-modifying enzymes: encrypting an enigmatic epigenetic code.
  Curr Opin Struct Biol, 16, 753-760.  
17108971 J.Huang, L.Perez-Burgos, B.J.Placek, R.Sengupta, M.Richter, J.A.Dorsey, S.Kubicek, S.Opravil, T.Jenuwein, and S.L.Berger (2006).
Repression of p53 activity by Smyd2-mediated methylation.
  Nature, 444, 629-632.  
16581806 K.J.Riley, L.A.Cassiday, A.Kumar, and L.J.Maher (2006).
Recognition of RNA by the p53 tumor suppressor protein in the yeast three-hybrid system.
  RNA, 12, 620-630.  
17150106 L.Zhang, L.Nie, and C.G.Maki (2006).
P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity.
  Mol Cancer, 5, 68.  
17092350 M.Ducasse, and M.A.Brown (2006).
Epigenetic aberrations and cancer.
  Mol Cancer, 5, 60.  
16601750 M.F.Lavin, and N.Gueven (2006).
The complexity of p53 stabilization and activation.
  Cell Death Differ, 13, 941-950.  
16963494 M.Stabell, R.Eskeland, M.Bjørkmo, J.Larsson, R.B.Aalen, A.Imhof, and A.Lambertsson (2006).
The Drosophila G9a gene encodes a multi-catalytic histone methyltransferase required for normal development.
  Nucleic Acids Res, 34, 4609-4621.  
16575405 O.Laptenko, and C.Prives (2006).
Transcriptional regulation by p53: one protein, many possibilities.
  Cell Death Differ, 13, 951-961.  
16936826 P.M.Dehé, and V.Géli (2006).
The multiple faces of Set1.
  Biochem Cell Biol, 84, 536-548.  
16430779 P.Sharma, R.D.Senthilkumar, V.Brahmachari, E.Sundaramoorthy, A.Mahajan, A.Sharma, and S.Sengupta (2006).
Mining literature for a comprehensive pathway analysis: a case study for retrieval of homocysteine related genes for genetic and epigenetic studies.
  Lipids Health Dis, 5, 1.  
16680460 T.B.Tomasi, W.J.Magner, and A.N.Khan (2006).
Epigenetic regulation of immune escape genes in cancer.
  Cancer Immunol Immunother, 55, 1159-1184.  
16857008 T.Jenuwein (2006).
The epigenetic magic of histone lysine methylation.
  FEBS J, 273, 3121-3135.  
16293626 V.Basile, R.Mantovani, and C.Imbriano (2006).
DNA damage promotes histone deacetylase 4 nuclear localization and repression of G2/M promoters, via p53 C-terminal lysines.
  J Biol Chem, 281, 2347-2357.  
17189186 Y.Tang, J.Luo, W.Zhang, and W.Gu (2006).
Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis.
  Mol Cell, 24, 827-839.  
15837201 A.Friedler, D.B.Veprintsev, S.M.Freund, K.I.von Glos, and A.R.Fersht (2005).
Modulation of binding of DNA to the C-terminal domain of p53 by acetylation.
  Structure, 13, 629-636.  
15933069 B.Xiao, C.Jing, G.Kelly, P.A.Walker, F.W.Muskett, T.A.Frenkiel, S.R.Martin, K.Sarma, D.Reinberg, S.J.Gamblin, and J.R.Wilson (2005).
Specificity and mechanism of the histone methyltransferase Pr-Set7.
  Genes Dev, 19, 1444-1454.
PDB code: 2bqz
16007140 C.Schwerk, and K.Schulze-Osthoff (2005).
Methyltransferase inhibition induces p53-dependent apoptosis and a novel form of cell death.
  Oncogene, 24, 7002-7011.  
16247734 H.Iwabata, M.Yoshida, and Y.Komatsu (2005).
Proteomic analysis of organ-specific post-translational lysine-acetylation and -methylation in mice by use of anti-acetyllysine and -methyllysine mouse monoclonal antibodies.
  Proteomics, 5, 4653-4664.  
15882624 I.H.Su, M.W.Dobenecker, E.Dickinson, M.Oser, A.Basavaraj, R.Marqueron, A.Viale, D.Reinberg, C.Wülfing, and A.Tarakhovsky (2005).
Polycomb group protein ezh2 controls actin polymerization and cell signaling.
  Cell, 121, 425-436.  
16126384 J.C.Nolz, T.S.Gomez, and D.D.Billadeau (2005).
The Ezh2 methyltransferase complex: actin up in the cytosol.
  Trends Cell Biol, 15, 514-517.  
15933070 J.F.Couture, E.Collazo, J.S.Brunzelle, and R.C.Trievel (2005).
Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase.
  Genes Dev, 19, 1455-1465.
PDB code: 1zkk
16141209 J.Francis, S.K.Chakrabarti, J.C.Garmey, and R.G.Mirmira (2005).
Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II elongation during activation of insulin transcription.
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16006521 K.A.Krummel, C.J.Lee, F.Toledo, and G.M.Wahl (2005).
The C-terminal lysines fine-tune P53 stress responses in a mouse model but are not required for stability control or transactivation.
  Proc Natl Acad Sci U S A, 102, 10188-10193.  
16173079 K.Zhang, and S.Y.Dent (2005).
Histone modifying enzymes and cancer: going beyond histones.
  J Cell Biochem, 96, 1137-1148.  
15964796 L.Feng, T.Lin, H.Uranishi, W.Gu, and Y.Xu (2005).
Functional analysis of the roles of posttranslational modifications at the p53 C terminus in regulating p53 stability and activity.
  Mol Cell Biol, 25, 5389-5395.  
16225687 P.Z.Kozbial, and A.R.Mushegian (2005).
Natural history of S-adenosylmethionine-binding proteins.
  BMC Struct Biol, 5, 19.  
16086857 S.C.Dillon, X.Zhang, R.C.Trievel, and X.Cheng (2005).
The SET-domain protein superfamily: protein lysine methyltransferases.
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15869391 X.Cheng, R.E.Collins, and X.Zhang (2005).
Structural and sequence motifs of protein (histone) methylation enzymes.
  Annu Rev Biophys Biomol Struct, 34, 267-294.  
15661530 X.Lu (2005).
p53: a heavily dictated dictator of life and death.
  Curr Opin Genet Dev, 15, 27-33.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.