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PDBsum entry 1jsu

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protein ligands Protein-protein interface(s) links
Complex (transferase/cyclin/inhibitor) PDB id
1jsu
Jmol
Contents
Protein chains
286 a.a. *
258 a.a. *
69 a.a. *
Ligands
SO4
Waters ×197
* Residue conservation analysis
PDB id:
1jsu
Name: Complex (transferase/cyclin/inhibitor)
Title: P27(kip1)/cyclin a/cdk2 complex
Structure: Cyclin-dependent kinase-2. Chain: a. Synonym: cdk2. Engineered: yes. Mutation: yes. Cyclin a. Chain: b. Fragment: residues 173 - 432. Engineered: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: sf9. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Other_details: cyclin a-bound form phosphorylated on thr 160 in vitro using a cdk-activating kinase consisting of
Biol. unit: Trimer (from PQS)
Resolution:
2.30Å     R-factor:   0.192     R-free:   0.260
Authors: A.A.Russo,P.D.Jeffrey,N.P.Pavletich
Key ref: A.A.Russo et al. (1996). Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex. Nature, 382, 325-331. PubMed id: 8684460 DOI: 10.1038/382325a0
Date:
03-Jul-96     Release date:   29-Jul-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
286 a.a.*
Protein chain
Pfam   ArchSchema ?
P20248  (CCNA2_HUMAN) -  Cyclin-A2
Seq:
Struc:
432 a.a.
258 a.a.
Protein chain
Pfam   ArchSchema ?
P46527  (CDN1B_HUMAN) -  Cyclin-dependent kinase inhibitor 1B
Seq:
Struc:
198 a.a.
69 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.2.7.11.22  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cyclin-dependent protein kinase holoenzyme complex   15 terms 
  Biological process     regulation of gene silencing   31 terms 
  Biochemical function     nucleotide binding     14 terms  

 

 
    reference    
 
 
DOI no: 10.1038/382325a0 Nature 382:325-331 (1996)
PubMed id: 8684460  
 
 
Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex.
A.A.Russo, P.D.Jeffrey, A.K.Patten, J.Massagué, N.P.Pavletich.
 
  ABSTRACT  
 
The crystal structure of the human p27Kip1 kinase inhibitory domain bound to the phosphorylated cyclin A-cyclin-dependent kinase 2 (Cdk2) complex has been determined at 2.3 angstrom. p27Kip1 binds the complex as an extended structure interacting with both cyclin A and Cdk2. On cyclin A, it binds in a groove formed by conserved cyclin box residues. On Cdk2, it binds and rearranges the amino-terminal lobe and also inserts into the catalytic cleft, mimicking ATP.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21423160 G.W.Daughdrill (2011).
Protein dynamics: bridging the gap.
  Nat Chem Biol, 7, 193-194.  
21539793 S.Brocca, L.Testa, F.Sobott, M.Samalikova, A.Natalello, E.Papaleo, M.Lotti, L.De Gioia, S.M.Doglia, L.Alberghina, and R.Grandori (2011).
Compaction properties of an intrinsically disordered protein: sic1 and its kinase-inhibitor domain.
  Biophys J, 100, 2243-2252.  
21358637 Y.Wang, J.C.Fisher, R.Mathew, L.Ou, S.Otieno, J.Sublet, L.Xiao, J.Chen, M.F.Roussel, and R.W.Kriwacki (2011).
Intrinsic disorder mediates the diverse regulatory functions of the Cdk inhibitor p21.
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20639412 A.Ofir, and D.Kornitzer (2010).
Candida albicans cyclin Clb4 carries S-phase cyclin activity.
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20838604 C.V.Kuny, K.Chinchilla, M.R.Culbertson, and R.F.Kalejta (2010).
Cyclin-dependent kinase-like function is shared by the beta- and gamma- subset of the conserved herpesvirus protein kinases.
  PLoS Pathog, 6, 0.  
20606006 D.H.Kim, V.N.Budhavarapu, C.R.Herrera, H.W.Nam, Y.S.Kim, and P.R.Yew (2010).
The CRL4Cdt2 ubiquitin ligase mediates the proteolysis of cyclin-dependent kinase inhibitor Xic1 through a direct association with PCNA.
  Mol Cell Biol, 30, 4120-4133.  
20133681 D.Varma, A.Dawn, A.Ghosh-Roy, S.J.Weil, K.M.Ori-McKenney, Y.Zhao, J.Keen, R.B.Vallee, and J.C.Williams (2010).
Development and application of in vivo molecular traps reveals that dynein light chain occupancy differentially affects dynein-mediated processes.
  Proc Natl Acad Sci U S A, 107, 3493-3498.  
20133761 G.Pascreau, F.Eckerdt, M.E.Churchill, and J.L.Maller (2010).
Discovery of a distinct domain in cyclin A sufficient for centrosomal localization independently of Cdk binding.
  Proc Natl Acad Sci U S A, 107, 2932-2937.  
  20565244 J.Madhavan, K.Mallikarjuna, K.Vikas, R.George, R.Bremner, and G.Kumaramanickavel (2010).
CDKN1C (p57KIP2) mRNA expression in human retinoblastomas.
  Ophthalmic Genet, 31, 141-146.  
20516199 K.Nestoras, A.H.Mohammed, A.S.Schreurs, O.Fleck, A.T.Watson, M.Poitelea, C.O'Shea, C.Chahwan, C.Holmberg, B.B.Kragelund, O.Nielsen, M.Osborne, A.M.Carr, and C.Liu (2010).
Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms.
  Genes Dev, 24, 1145-1159.  
20556825 M.Kjaergaard, A.B.Nørholm, R.Hendus-Altenburger, S.F.Pedersen, F.M.Poulsen, and B.B.Kragelund (2010).
Temperature-dependent structural changes in intrinsically disordered proteins: formation of alpha-helices or loss of polyproline II?
  Protein Sci, 19, 1555-1564.  
20714778 M.L.Hegde, T.K.Hazra, and S.Mitra (2010).
Functions of disordered regions in mammalian early base excision repair proteins.
  Cell Mol Life Sci, 67, 3573-3587.  
19722269 P.Radivojac, V.Vacic, C.Haynes, R.R.Cocklin, A.Mohan, J.W.Heyen, M.G.Goebl, and L.M.Iakoucheva (2010).
Identification, analysis, and prediction of protein ubiquitination sites.
  Proteins, 78, 365-380.  
20663915 R.L.Ferguson, G.Pascreau, and J.L.Maller (2010).
The cyclin A centrosomal localization sequence recruits MCM5 and Orc1 to regulate centrosome reduplication.
  J Cell Sci, 123, 2743-2749.  
20805515 S.Chakrabortee, F.Meersman, G.S.Kaminski Schierle, C.W.Bertoncini, B.McGee, C.F.Kaminski, and A.Tunnacliffe (2010).
Catalytic and chaperone-like functions in an intrinsically disordered protein associated with desiccation tolerance.
  Proc Natl Acad Sci U S A, 107, 16084-16089.  
20824794 S.Molatore, I.Marinoni, M.Lee, E.Pulz, M.R.Ambrosio, E.C.degli Uberti, M.C.Zatelli, and N.S.Pellegata (2010).
A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization.
  Hum Mutat, 31, E1825-E1835.  
20535204 T.H.Tahirov, N.D.Babayeva, K.Varzavand, J.J.Cooper, S.C.Sedore, and D.H.Price (2010).
Crystal structure of HIV-1 Tat complexed with human P-TEFb.
  Nature, 465, 747-751.
PDB codes: 3mi9 3mia
19412530 B.Mészáros, I.Simon, and Z.Dosztányi (2009).
Prediction of protein binding regions in disordered proteins.
  PLoS Comput Biol, 5, e1000376.  
19470474 C.G.Mullighan, J.Zhang, R.C.Harvey, J.R.Collins-Underwood, B.A.Schulman, L.A.Phillips, S.K.Tasian, M.L.Loh, X.Su, W.Liu, M.Devidas, S.R.Atlas, I.M.Chen, R.J.Clifford, D.S.Gerhard, W.L.Carroll, G.H.Reaman, M.Smith, J.R.Downing, S.P.Hunger, and C.L.Willman (2009).
JAK mutations in high-risk childhood acute lymphoblastic leukemia.
  Proc Natl Acad Sci U S A, 106, 9414-9418.  
19447088 C.L.Frank, and L.H.Tsai (2009).
Alternative functions of core cell cycle regulators in neuronal migration, neuronal maturation, and synaptic plasticity.
  Neuron, 62, 312-326.  
19918049 F.Villa, P.Capasso, M.Tortorici, F.Forneris, A.de Marco, A.Mattevi, and A.Musacchio (2009).
Crystal structure of the catalytic domain of Haspin, an atypical kinase implicated in chromatin organization.
  Proc Natl Acad Sci U S A, 106, 20204-20209.
PDB code: 2wb8
19472269 G.Kontopidis, M.J.Andrews, C.McInnes, A.Plater, L.Innes, S.Renachowski, A.Cowan, and P.M.Fischer (2009).
Truncation and optimisation of peptide inhibitors of cyclin-dependent kinase 2-cyclin a through structure-guided design.
  ChemMedChem, 4, 1120-1128.
PDB codes: 2wev 2wfy 2whb
19665013 J.Kisielewska, R.Philipova, J.Y.Huang, and M.Whitaker (2009).
MAP kinase dependent cyclinE/cdk2 activity promotes DNA replication in early sea urchin embryos.
  Dev Biol, 334, 383-394.  
19887899 J.Lee, and S.S.Kim (2009).
The function of p27 KIP1 during tumor development.
  Exp Mol Med, 41, 765-771.  
19218424 K.Streckfuss-Bömeke, F.Schulze, B.Herzog, E.Scholz, and G.H.Braus (2009).
Degradation of Saccharomyces cerevisiae transcription factor Gcn4 requires a C-terminal nuclear localization signal in the cyclin Pcl5.
  Eukaryot Cell, 8, 496-510.  
19308324 K.Teilum, J.G.Olsen, and B.B.Kragelund (2009).
Functional aspects of protein flexibility.
  Cell Mol Life Sci, 66, 2231-2247.  
19039815 M.Orzáez, A.Gortat, L.Mondragón, O.Bachs, and E.Pérez-Payá (2009).
ATP-noncompetitive inhibitors of CDK-cyclin complexes.
  ChemMedChem, 4, 19-24.  
19710018 P.Corsino, N.Horenstein, D.Ostrov, T.Rowe, M.Law, A.Barrett, G.Aslanidi, W.D.Cress, and B.Law (2009).
A novel class of cyclin-dependent kinase inhibitors identified by molecular docking act through a unique mechanism.
  J Biol Chem, 284, 29945-29955.  
19280601 S.Brocca, M.Samalíková, V.N.Uversky, M.Lotti, M.Vanoni, L.Alberghina, and R.Grandori (2009).
Order propensity of an intrinsically disordered protein, the cyclin-dependent-kinase inhibitor Sic1.
  Proteins, 76, 731-746.  
19237555 T.Takaki, A.Echalier, N.R.Brown, T.Hunt, J.A.Endicott, and M.E.Noble (2009).
The structure of CDK4/cyclin D3 has implications for models of CDK activation.
  Proc Natl Acad Sci U S A, 106, 4171-4176.
PDB code: 3g33
  19029828 A.Forget, O.Ayrault, W.den Besten, M.L.Kuo, C.J.Sherr, and M.F.Roussel (2008).
Differential post-transcriptional regulation of two Ink4 proteins, p18 Ink4c and p19 Ink4d.
  Cell Cycle, 7, 3737-3746.  
18831774 A.K.Dunker, C.J.Oldfield, J.Meng, P.Romero, J.Y.Yang, J.W.Chen, V.Vacic, Z.Obradovic, and V.N.Uversky (2008).
The unfoldomics decade: an update on intrinsically disordered proteins.
  BMC Genomics, 9, S1.  
18347590 A.K.Dunker, and V.N.Uversky (2008).
Signal transduction via unstructured protein conduits.
  Nat Chem Biol, 4, 229-230.  
18266114 A.Philpott, and P.R.Yew (2008).
The Xenopus cell cycle: an overview.
  Mol Biotechnol, 39, 9.  
18177895 C.A.Galea, A.Nourse, Y.Wang, S.G.Sivakolundu, W.T.Heller, and R.W.Kriwacki (2008).
Role of intrinsic flexibility in signal transduction mediated by the cell cycle regulator, p27 Kip1.
  J Mol Biol, 376, 827-838.  
18627125 C.A.Galea, Y.Wang, S.G.Sivakolundu, and R.W.Kriwacki (2008).
Regulation of cell division by intrinsically unstructured proteins: intrinsic flexibility, modularity, and signaling conduits.
  Biochemistry, 47, 7598-7609.  
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.  
18558651 F.Hu, Y.Gan, and O.M.Aparicio (2008).
Identification of Clb2 residues required for Swe1 regulation of Clb2-Cdc28 in Saccharomyces cerevisiae.
  Genetics, 179, 863-874.  
18042686 I.Bártová, J.Koca, and M.Otyepka (2008).
Functional flexibility of human cyclin-dependent kinase-2 and its evolutionary conservation.
  Protein Sci, 17, 22-33.  
18354415 I.M.Chu, L.Hengst, and J.M.Slingerland (2008).
The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy.
  Nat Rev Cancer, 8, 253-267.  
19029897 K.Anand, A.Schulte, K.Vogel-Bachmayr, K.Scheffzek, and M.Geyer (2008).
Structural insights into the cyclin T1-Tat-TAR RNA transcription activation complex from EIAV.
  Nat Struct Mol Biol, 15, 1287-1292.
PDB code: 2w2h
18331637 K.Manikandan, D.Pal, S.Ramakumar, N.E.Brener, S.S.Iyengar, and G.Seetharaman (2008).
Functionally important segments in proteins dissected using Gene Ontology and geometric clustering of peptide fragments.
  Genome Biol, 9, R52.  
17908796 M.K.James, A.Ray, D.Leznova, and S.W.Blain (2008).
Differential modification of p27Kip1 controls its cyclin D-cdk4 inhibitory activity.
  Mol Cell Biol, 28, 498-510.  
18619997 M.S.Cortese, V.N.Uversky, and A.K.Dunker (2008).
Intrinsic disorder in scaffold proteins: getting more from less.
  Prog Biophys Mol Biol, 98, 85.  
18794371 S.Aviram, E.Simon, T.Gildor, F.Glaser, and D.Kornitzer (2008).
Autophosphorylation-induced degradation of the Pho85 cyclin Pcl5 is essential for response to amino acid limitation.
  Mol Cell Biol, 28, 6858-6869.  
18566585 S.Baumli, G.Lolli, E.D.Lowe, S.Troiani, L.Rusconi, A.N.Bullock, J.E.Debreczeni, S.Knapp, and L.N.Johnson (2008).
The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation.
  EMBO J, 27, 1907-1918.
PDB codes: 2ivx 3blh 3blq 3blr
18059263 Y.S.Lee, K.Huang, F.A.Quiocho, and E.K.O'Shea (2008).
Molecular basis of cyclin-CDK-CKI regulation by reversible binding of an inositol pyrophosphate.
  Nat Chem Biol, 4, 25-32.  
18180298 Z.Li, C.Wang, X.Jiao, S.Katiyar, M.C.Casimiro, G.C.Prendergast, M.J.Powell, and R.G.Pestell (2008).
Alternate cyclin D1 mRNA splicing modulates p27KIP1 binding and cell migration.
  J Biol Chem, 283, 7007-7015.  
17626791 A.Besson, H.C.Hwang, S.Cicero, S.L.Donovan, M.Gurian-West, D.Johnson, B.E.Clurman, M.A.Dyer, and J.M.Roberts (2007).
Discovery of an oncogenic activity in p27Kip1 that causes stem cell expansion and a multiple tumor phenotype.
  Genes Dev, 21, 1731-1746.  
17373709 G.Lolli, and L.N.Johnson (2007).
Recognition of Cdk2 by Cdk7.
  Proteins, 67, 1048-1059.
PDB code: 2hic
17342741 G.M.Buchold, P.L.Magyar, R.Arumugam, M.M.Lee, and D.A.O'Brien (2007).
p19Ink4d and p18Ink4c cyclin-dependent kinase inhibitors in the male reproductive axis.
  Mol Reprod Dev, 74, 997.  
17254967 I.Chu, J.Sun, A.Arnaout, H.Kahn, W.Hanna, S.Narod, P.Sun, C.K.Tan, L.Hengst, and J.Slingerland (2007).
p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2.
  Cell, 128, 281-294.  
17292838 J.Eswaran, W.H.Lee, J.E.Debreczeni, P.Filippakopoulos, A.Turnbull, O.Fedorov, S.W.Deacon, J.R.Peterson, and S.Knapp (2007).
Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs.
  Structure, 15, 201-213.
PDB codes: 2bva 2c30 2cdz 2f57
17540406 K.Anand, A.Schulte, K.Fujinaga, K.Scheffzek, and M.Geyer (2007).
Cyclin box structure of the P-TEFb subunit cyclin T1 derived from a fusion complex with EIAV tat.
  J Mol Biol, 370, 826-836.
PDB code: 2pk2
17169370 K.Baek, R.S.Brown, G.Birrane, and J.A.Ladias (2007).
Crystal structure of human cyclin K, a positive regulator of cyclin-dependent kinase 9.
  J Mol Biol, 366, 563-573.
PDB code: 2i53
18042456 K.Huang, I.Ferrin-O'Connell, W.Zhang, G.A.Leonard, E.K.O'Shea, and F.A.Quiocho (2007).
Structure of the Pho85-Pho80 CDK-cyclin complex of the phosphate-responsive signal transduction pathway.
  Mol Cell, 28, 614-623.
PDB codes: 2pk9 2pmi
17409683 K.Nitta, T.Kawano, S.Sugawara, and M.Hosono (2007).
[Regulation of globotriaosylceramide (Gb3)-mediated signal transduction by rhamnose-binding lectin]
  Yakugaku Zasshi, 127, 553-561.  
17371838 L.E.Giono, and J.J.Manfredi (2007).
Mdm2 is required for inhibition of Cdk2 activity by p21, thereby contributing to p53-dependent cell cycle arrest.
  Mol Cell Biol, 27, 4166-4178.  
17614281 M.A.Keaton, E.S.Bardes, A.R.Marquitz, C.D.Freel, T.R.Zyla, J.Rudolph, and D.J.Lew (2007).
Differential susceptibility of yeast S and M phase CDK complexes to inhibitory tyrosine phosphorylation.
  Curr Biol, 17, 1181-1189.  
17254966 M.Grimmler, Y.Wang, T.Mund, Z.Cilensek, E.M.Keidel, M.B.Waddell, H.Jäkel, M.Kullmann, R.W.Kriwacki, and L.Hengst (2007).
Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases.
  Cell, 128, 269-280.  
17705877 N.Sugaya, K.Ikeda, T.Tashiro, S.Takeda, J.Otomo, Y.Ishida, A.Shiratori, A.Toyoda, H.Noguchi, T.Takeda, S.Kuhara, Y.Sakaki, and T.Iwayanagi (2007).
An integrative in silico approach for discovering candidates for drug-targetable protein-protein interactions in interactome data.
  BMC Pharmacol, 7, 10.  
17254963 P.Kaldis (2007).
Another piece of the p27Kip1 puzzle.
  Cell, 128, 241-244.  
17403142 Q.Wei, T.Eviatar-Ribak, W.K.Miskimins, and R.Miskimins (2007).
Galectin-4 is involved in p27-mediated activation of the myelin basic protein promoter.
  J Neurochem, 101, 1214-1223.  
17488107 V.Vacic, C.J.Oldfield, A.Mohan, P.Radivojac, M.S.Cortese, V.N.Uversky, and A.K.Dunker (2007).
Characterization of molecular recognition features, MoRFs, and their binding partners.
  J Proteome Res, 6, 2351-2366.  
17218276 Y.Geng, Y.M.Lee, M.Welcker, J.Swanger, A.Zagozdzon, J.D.Winer, J.M.Roberts, P.Kaldis, B.E.Clurman, and P.Sicinski (2007).
Kinase-independent function of cyclin E.
  Mol Cell, 25, 127-139.  
17431791 Y.T.Oh, K.H.Chun, B.D.Park, J.S.Choi, and S.K.Lee (2007).
Regulation of cyclin-dependent kinase inhibitor p21WAF1/CIP1 by protein kinase Cdelta-mediated phosphorylation.
  Apoptosis, 12, 1339-1347.  
17317670 Y.Tu, W.Wu, T.Wu, Z.Cao, R.Wilkins, B.H.Toh, M.E.Cooper, and Z.Chai (2007).
Antiproliferative autoantigen CDA1 transcriptionally up-regulates p21(Waf1/Cip1) by activating p53 and MEK/ERK1/2 MAPK pathways.
  J Biol Chem, 282, 11722-11731.  
16508017 A.Järviluoma, E.S.Child, G.Sarek, P.Sirimongkolkasem, G.Peters, P.M.Ojala, and D.J.Mann (2006).
Phosphorylation of the cyclin-dependent kinase inhibitor p21Cip1 on serine 130 is essential for viral cyclin-mediated bypass of a p21Cip1-imposed G1 arrest.
  Mol Cell Biol, 26, 2430-2440.  
16374872 J.Bonet, G.Caltabiano, A.K.Khan, M.A.Johnston, C.Corbí, A.Gómez, X.Rovira, J.Teyra, and J.Villà-Freixa (2006).
The role of residue stability in transient protein-protein interactions involved in enzymatic phosphate hydrolysis. A computational study.
  Proteins, 63, 65-77.  
16921029 J.J.Miller, M.K.Summers, D.V.Hansen, M.V.Nachury, N.L.Lehman, A.Loktev, and P.K.Jackson (2006).
Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor.
  Genes Dev, 20, 2410-2420.  
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
16515645 J.Watanabe, K.Watanabe, T.Jobo, Y.Kamata, M.Kawaguchi, M.Imai, I.Okayasu, and H.Kuramoto (2006).
Significance of p27 as a predicting marker for medroxyprogesterone acetate therapy against endometrial endometrioid adenocarcinoma.
  Int J Gynecol Cancer, 16, 452-457.  
16707497 K.Y.Cheng, M.E.Noble, V.Skamnaki, N.R.Brown, E.D.Lowe, L.Kontogiannis, K.Shen, P.A.Cole, G.Siligardi, and L.N.Johnson (2006).
The role of the phospho-CDK2/cyclin A recruitment site in substrate recognition.
  J Biol Chem, 281, 23167-23179.
PDB codes: 2cch 2cci
16782892 L.Bockstaele, H.Kooken, F.Libert, S.Paternot, J.E.Dumont, Y.de Launoit, P.P.Roger, and K.Coulonval (2006).
Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK "inhibitors".
  Mol Cell Biol, 26, 5070-5085.  
17092340 L.Bockstaele, K.Coulonval, H.Kooken, S.Paternot, and P.P.Roger (2006).
Regulation of CDK4.
  Cell Div, 1, 25.  
17013388 L.Li, Y.Iwamoto, A.Berezovskaya, and V.A.Boussiotis (2006).
A pathway regulated by cell cycle inhibitor p27Kip1 and checkpoint inhibitor Smad3 is involved in the induction of T cell tolerance.
  Nat Immunol, 7, 1157-1165.  
16807909 L.Nguyen, L.Borgs, R.Vandenbosch, J.M.Mangin, P.Beukelaers, G.Moonen, V.Gallo, B.Malgrange, and S.Belachew (2006).
The Yin and Yang of cell cycle progression and differentiation in the oligodendroglial lineage.
  Ment Retard Dev Disabil Res Rev, 12, 85-96.  
16780593 L.P.Nacusi, and R.J.Sheaff (2006).
Akt1 sequentially phosphorylates p27kip1 within a conserved but non-canonical region.
  Cell Div, 1, 11.  
17051658 M.J.Andrews, G.Kontopidis, C.McInnes, A.Plater, L.Innes, A.Cowan, P.Jewsbury, and P.M.Fischer (2006).
REPLACE: a strategy for iterative design of cyclin-binding groove inhibitors.
  Chembiochem, 7, 1909-1915.
PDB codes: 2uue 2v22
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Low p27 expression correlates with poor prognosis for patients with oral tongue squamous cell carcinoma.
  Cancer, 85, 1011-1017.  
10064597 H.Yasukawa, H.Misawa, H.Sakamoto, M.Masuhara, A.Sasaki, T.Wakioka, S.Ohtsuka, T.Imaizumi, T.Matsuda, J.N.Ihle, and A.Yoshimura (1999).
The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop.
  EMBO J, 18, 1309-1320.  
10607671 J.A.Endicott, M.E.Noble, and J.A.Tucker (1999).
Cyclin-dependent kinases: inhibition and substrate recognition.
  Curr Opin Struct Biol, 9, 738-744.  
  10091657 J.A.Hauer, P.Barthe, S.S.Taylor, J.Parello, and A.Padilla (1999).
Two well-defined motifs in the cAMP-dependent protein kinase inhibitor (PKIalpha) correlate with inhibitory and nuclear export function.
  Protein Sci, 8, 545-553.  
  9858585 J.M.Gudas, M.Payton, S.Thukral, E.Chen, M.Bass, M.O.Robinson, and S.Coats (1999).
Cyclin E2, a novel G1 cyclin that binds Cdk2 and is aberrantly expressed in human cancers.
  Mol Cell Biol, 19, 612-622.  
10428024 J.M.Roberts (1999).
Evolving ideas about cyclins.
  Cell, 98, 129-132.  
  10207115 J.Mitra, C.Y.Dai, K.Somasundaram, W.S.El-Deiry, K.Satyamoorthy, M.Herlyn, and G.H.Enders (1999).
Induction of p21(WAF1/CIP1) and inhibition of Cdk2 mediated by the tumor suppressor p16(INK4a).
  Mol Cell Biol, 19, 3916-3928.  
  10330164 L.K.Felzien, S.Farrell, J.C.Betts, R.Mosavin, and G.J.Nabel (1999).
Specificity of cyclin E-Cdk2, TFIIB, and E1A interactions with a common domain of the p300 coactivator.
  Mol Cell Biol, 19, 4241-4246.  
10075928 M.Cheng, P.Olivier, J.A.Diehl, M.Fero, M.F.Roussel, J.M.Roberts, and C.J.Sherr (1999).
The p21(Cip1) and p27(Kip1) CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts.
  EMBO J, 18, 1571-1583.  
10025408 M.Huse, Y.G.Chen, J.Massagué, and J.Kuriyan (1999).
Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12.
  Cell, 96, 425-436.
PDB code: 1b6c
10455103 M.Taulés, A.Rodríguez-Vilarrupla, E.Rius, J.M.Estanyol, O.Casanovas, D.B.Sacks, E.Pérez-Payá, O.Bachs, and N.Agell (1999).
Calmodulin binds to p21(Cip1) and is involved in the regulation of its nuclear localization.
  J Biol Chem, 274, 24445-24448.  
  10207089 M.Tsubari, J.Taipale, E.Tiihonen, J.Keski-Oja, and M.Laiho (1999).
Hepatocyte growth factor releases mink epithelial cells from transforming growth factor beta1-induced growth arrest by restoring Cdk6 expression and cyclin E-associated Cdk2 activity.
  Mol Cell Biol, 19, 3654-3663.  
10085115 N.R.Brown, M.E.Noble, A.M.Lawrie, M.C.Morris, P.Tunnah, G.Divita, L.N.Johnson, and J.A.Endicott (1999).
Effects of phosphorylation of threonine 160 on cyclin-dependent kinase 2 structure and activity.
  J Biol Chem, 274, 8746-8756.
PDB codes: 1b38 1b39
  9891042 P.D.Adams, X.Li, W.R.Sellers, K.B.Baker, X.Leng, J.W.Harper, Y.Taya, and W.G.Kaelin (1999).
Retinoblastoma protein contains a C-terminal motif that targets it for phosphorylation by cyclin-cdk complexes.
  Mol Cell Biol, 19, 1068-1080.  
10322109 P.M.Holland, and J.A.Cooper (1999).
Protein modification: docking sites for kinases.
  Curr Biol, 9, R329-R331.  
  10027389 R.V.Lloyd, L.A.Erickson, L.Jin, E.Kulig, X.Qian, J.C.Cheville, and B.W.Scheithauer (1999).
p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers.
  Am J Pathol, 154, 313-323.  
10074425 S.Coats, P.Whyte, M.L.Fero, S.Lacy, G.Chung, E.Randel, E.Firpo, and J.M.Roberts (1999).
A new pathway for mitogen-dependent cdk2 regulation uncovered in p27(Kip1)-deficient cells.
  Curr Biol, 9, 163-173.  
10589678 S.Ohnuma, A.Philpott, K.Wang, C.E.Holt, and W.A.Harris (1999).
p27Xic1, a Cdk inhibitor, promotes the determination of glial cells in Xenopus retina.
  Cell, 99, 499-510.  
9892642 T.Ma, N.Zou, B.Y.Lin, L.T.Chow, and J.W.Harper (1999).
Interaction between cyclin-dependent kinases and human papillomavirus replication-initiation protein E1 is required for efficient viral replication.
  Proc Natl Acad Sci U S A, 96, 382-387.  
10368294 U.Schulze-Gahmen, J.U.Jung, and S.H.Kim (1999).
Crystal structure of a viral cyclin, a positive regulator of cyclin-dependent kinase 6.
  Structure, 7, 245-254.
PDB code: 1bu2
10517868 W.G.Kaelin (1999).
Functions of the retinoblastoma protein.
  Bioessays, 21, 950-958.  
10200261 Y.N.Chen, S.K.Sharma, T.M.Ramsey, L.Jiang, M.S.Martin, K.Baker, P.D.Adams, K.W.Bair, and W.G.Kaelin (1999).
Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists.
  Proc Natl Acad Sci U S A, 96, 4325-4329.  
  9418909 A.B.Niculescu, X.Chen, M.Smeets, L.Hengst, C.Prives, and S.I.Reed (1998).
Effects of p21(Cip1/Waf1) at both the G1/S and the G2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication.
  Mol Cell Biol, 18, 629-643.  
9724724 B.A.Schulman, D.L.Lindstrom, and E.Harlow (1998).
Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A.
  Proc Natl Acad Sci U S A, 95, 10453-10458.  
9860936 B.E.Clurman, and P.Porter (1998).
New insights into the tumor suppression function of P27(kip1)
  Proc Natl Acad Sci U S A, 95, 15158-15160.  
9646865 D.Barford, A.K.Das, and M.P.Egloff (1998).
The structure and mechanism of protein phosphatases: insights into catalysis and regulation.
  Annu Rev Biophys Biomol Struct, 27, 133-164.  
  9584169 D.Huang, J.Moffat, W.A.Wilson, L.Moore, C.Cheng, P.J.Roach, and B.Andrews (1998).
Cyclin partners determine Pho85 protein kinase substrate specificity in vitro and in vivo: control of glycogen biosynthesis by Pcl8 and Pcl10.
  Mol Cell Biol, 18, 3289-3299.  
  9418890 D.I.Jeoung, L.J.Oehlen, and F.R.Cross (1998).
Cln3-associated kinase activity in Saccharomyces cerevisiae is regulated by the mating factor pathway.
  Mol Cell Biol, 18, 433-441.  
9741622 D.Liu, R.Ishima, K.I.Tong, S.Bagby, T.Kokubo, D.R.Muhandiram, L.E.Kay, Y.Nakatani, and M.Ikura (1998).
Solution structure of a TBP-TAF(II)230 complex: protein mimicry of the minor groove surface of the TATA box unwound by TBP.
  Cell, 94, 573-583.
PDB code: 1tba
  9528753 E.A.Musgrove, A.Swarbrick, C.S.Lee, A.L.Cornish, and R.L.Sutherland (1998).
Mechanisms of cyclin-dependent kinase inactivation by progestins.
  Mol Cell Biol, 18, 1812-1825.  
  9710622 E.Castaño, Y.Kleyner, and B.D.Dynlacht (1998).
Dual cyclin-binding domains are required for p107 to function as a kinase inhibitor.
  Mol Cell Biol, 18, 5380-5391.  
9551393 G.Wolf, R.Schroeder, F.Thaiss, F.N.Ziyadeh, U.Helmchen, and R.A.Stahl (1998).
Glomerular expression of p27Kip1 in diabetic db/db mouse: role of hyperglycemia.
  Kidney Int, 53, 869-879.  
9860976 H.Bastians, F.M.Townsley, and J.V.Ruderman (1998).
The cyclin-dependent kinase inhibitor p27(Kip1) induces N-terminal proteolytic cleavage of cyclin A.
  Proc Natl Acad Sci U S A, 95, 15374-15381.  
9753775 H.Wang, Q.Qi, P.Schorr, A.J.Cutler, W.L.Crosby, and L.C.Fowke (1998).
ICK1, a cyclin-dependent protein kinase inhibitor from Arabidopsis thaliana interacts with both Cdc2a and CycD3, and its expression is induced by abscisic acid.
  Plant J, 15, 501-510.  
9634691 J.A.Endicott, and M.E.Noble (1998).
Structural principles in cell-cycle control: beyond the CDKs.
  Structure, 6, 535-541.  
9430629 J.Lisztwan, A.Marti, H.Sutterlüty, M.Gstaiger, C.Wirbelauer, and W.Krek (1998).
Association of human CUL-1 and ubiquitin-conjugating enzyme CDC34 with the F-box protein p45(SKP2): evidence for evolutionary conservation in the subunit composition of the CDC34-SCF pathway.
  EMBO J, 17, 368-383.  
  9472014 J.Zhao, B.Dynlacht, T.Imai, T.Hori, and E.Harlow (1998).
Expression of NPAT, a novel substrate of cyclin E-CDK2, promotes S-phase entry.
  Genes Dev, 12, 456-461.  
9770473 K.Cai, and B.D.Dynlacht (1998).
Activity and nature of p21(WAF1) complexes during the cell cycle.
  Proc Natl Acad Sci U S A, 95, 12254-12259.  
15992004 K.R.Webster (1998).
The therapeutic potential of targeting the cell cycle.
  Expert Opin Investig Drugs, 7, 865-887.  
  9869641 L.Hengst, U.Göpfert, H.A.Lashuel, and S.I.Reed (1998).
Complete inhibition of Cdk/cyclin by one molecule of p21(Cip1).
  Genes Dev, 12, 3882-3888.  
  9832504 M.E.Garber, P.Wei, V.N.KewalRamani, T.P.Mayall, C.H.Herrmann, A.P.Rice, D.R.Littman, and K.A.Jones (1998).
The interaction between HIV-1 Tat and human cyclin T1 requires zinc and a critical cysteine residue that is not conserved in the murine CycT1 protein.
  Genes Dev, 12, 3512-3527.  
9461066 N.Q.McDonald, and G.Peters (1998).
Ankyrin for clues about the function of p16INK4a.
  Nat Struct Biol, 5, 85-88.  
  9725911 P.Kaldis, A.A.Russo, H.S.Chou, N.P.Pavletich, and M.J.Solomon (1998).
Human and yeast cdk-activating kinases (CAKs) display distinct substrate specificities.
  Mol Biol Cell, 9, 2545-2560.  
9733077 R.Tikoo, D.J.Osterhout, P.Casaccia-Bonnefil, P.Seth, A.Koff, and M.V.Chao (1998).
Ectopic expression of p27Kip1 in oligodendrocyte progenitor cells results in cell-cycle growth arrest.
  J Neurobiol, 36, 431-440.  
9437433 R.Venkataramani, K.Swaminathan, and R.Marmorstein (1998).
Crystal structure of the CDK4/6 inhibitory protein p18INK4c provides insights into ankyrin-like repeat structure/function and tumor-derived p16INK4 mutations.
  Nat Struct Biol, 5, 74-81.
PDB code: 1ihb
9468218 S.J.Robles, P.Shiyanov, G.T.Aristodemo, P.Raychaudhuri, and G.R.Adami (1998).
Site-directed mutant p21 proteins defective in both inhibition of E2F-regulated transcription and disruption of E2F-p130-cyclin-cdk2 complexes.
  DNA Cell Biol, 17, 9.  
  9566864 S.L.Tan, M.J.Gale, and M.G.Katze (1998).
Double-stranded RNA-independent dimerization of interferon-induced protein kinase PKR and inhibition of dimerization by the cellular P58IPK inhibitor.
  Mol Cell Biol, 18, 2431-2443.  
  9632802 S.Waga, and B.Stillman (1998).
Cyclin-dependent kinase inhibitor p21 modulates the DNA primer-template recognition complex.
  Mol Cell Biol, 18, 4177-4187.  
9624051 W.Feng, R.C.Ribeiro, R.L.Wagner, H.Nguyen, J.W.Apriletti, R.J.Fletterick, J.D.Baxter, P.J.Kushner, and B.L.West (1998).
Hormone-dependent coactivator binding to a hydrophobic cleft on nuclear receptors.
  Science, 280, 1747-1749.  
  9765467 X.Danthinne, K.Aoki, A.L.Kurachi, G.J.Nabel, and E.G.Nabel (1998).
Combination gene delivery of the cell cycle inhibitor p27 with thymidine kinase enhances prodrug cytotoxicity.
  J Virol, 72, 9201-9207.  
9632724 Y.Hashimoto, K.Kohri, Y.Kaneko, H.Morisaki, T.Kato, K.Ikeda, and M.Nakanishi (1998).
Critical role for the 310 helix region of p57(Kip2) in cyclin-dependent kinase 2 inhibition and growth suppression.
  J Biol Chem, 273, 16544-16550.  
  9199321 B.D.Dynlacht, K.Moberg, J.A.Lees, E.Harlow, and L.Zhu (1997).
Specific regulation of E2F family members by cyclin-dependent kinases.
  Mol Cell Biol, 17, 3867-3875.  
  17708915 C.Martin-Castellanos, and Moreno (1997).
Recent advances on cyclins, CDKs and CDK inhibitors.
  Trends Cell Biol, 7, 95-98.  
  9311733 D.O'Keefe, D.Dao, L.Zhao, R.Sanderson, D.Warburton, L.Weiss, K.Anyane-Yeboa, and B.Tycko (1997).
Coding mutations in p57KIP2 are present in some cases of Beckwith-Wiedemann syndrome but are rare or absent in Wilms tumors.
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9442875 D.O.Morgan (1997).
Cyclin-dependent kinases: engines, clocks, and microprocessors.
  Annu Rev Cell Dev Biol, 13, 261-291.  
9354760 D.Szwajkajzer, and J.Carey (1997).
Molecular and biological constraints on ligand-binding affinity and specificity.
  Biopolymers, 44, 181-198.  
  9271435 D.Woods, D.Parry, H.Cherwinski, E.Bosch, E.Lees, and M.McMahon (1997).
Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1.
  Mol Cell Biol, 17, 5598-5611.  
9118957 G.Andersen, D.Busso, A.Poterszman, J.R.Hwang, J.M.Wurtz, R.Ripp, J.C.Thierry, J.M.Egly, and D.Moras (1997).
The structure of cyclin H: common mode of kinase activation and specific features.
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  9372967 J.A.Diehl, and C.J.Sherr (1997).
A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK-activating kinase.
  Mol Cell Biol, 17, 7362-7374.  
  9284048 J.O.Funk, S.Waga, J.B.Harry, E.Espling, B.Stillman, and D.A.Galloway (1997).
Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein.
  Genes Dev, 11, 2090-2100.  
9311993 J.Vlach, S.Hennecke, and B.Amati (1997).
Phosphorylation-dependent degradation of the cyclin-dependent kinase inhibitor p27.
  EMBO J, 16, 5334-5344.  
9096291 K.Collins, T.Jacks, and N.P.Pavletich (1997).
The cell cycle and cancer.
  Proc Natl Acad Sci U S A, 94, 2776-2778.  
8999999 K.L.Ball, S.Lain, R.Fâhraeus, C.Smythe, and D.P.Lane (1997).
Cell-cycle arrest and inhibition of Cdk4 activity by small peptides based on the carboxy-terminal domain of p21WAF1.
  Curr Biol, 7, 71-80.  
  8972221 K.Zerfass-Thome, A.Schulze, W.Zwerschke, B.Vogt, K.Helin, J.Bartek, B.Henglein, and P.Jansen-Dürr (1997).
p27KIP1 blocks cyclin E-dependent transactivation of cyclin A gene expression.
  Mol Cell Biol, 17, 407-415.  
9363633 M.Arellano, and S.Moreno (1997).
Regulation of CDK/cyclin complexes during the cell cycle.
  Int J Biochem Cell Biol, 29, 559-573.  
9433129 M.E.Noble, J.A.Endicott, N.R.Brown, and L.N.Johnson (1997).
The cyclin box fold: protein recognition in cell-cycle and transcription control.
  Trends Biochem Sci, 22, 482-487.  
9155014 M.P.Egloff, D.F.Johnson, G.Moorhead, P.T.Cohen, P.Cohen, and D.Barford (1997).
Structural basis for the recognition of regulatory subunits by the catalytic subunit of protein phosphatase 1.
  EMBO J, 16, 1876-1887.  
  9199292 M.S.Woo, I.Sánchez, and B.D.Dynlacht (1997).
p130 and p107 use a conserved domain to inhibit cellular cyclin-dependent kinase activity.
  Mol Cell Biol, 17, 3566-3579.  
9261084 N.Narayana, S.Cox, X.Nguyen-huu, L.F.Ten Eyck, and S.S.Taylor (1997).
A binary complex of the catalytic subunit of cAMP-dependent protein kinase and adenosine further defines conformational flexibility.
  Structure, 5, 921-935.
PDB code: 1bkx
  9308962 P.Casaccia-Bonnefil, R.Tikoo, H.Kiyokawa, V.Friedrich, M.V.Chao, and A.Koff (1997).
Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1.
  Genes Dev, 11, 2335-2346.  
  9234691 P.Saha, Q.Eichbaum, E.D.Silberman, B.J.Mayer, and A.Dutta (1997).
p21CIP1 and Cdc25A: competition between an inhibitor and an activator of cyclin-dependent kinases.
  Mol Cell Biol, 17, 4338-4345.  
9026502 R.K.Assoian (1997).
Anchorage-dependent cell cycle progression.
  J Cell Biol, 136, 1-4.  
9024639 R.P.Fisher (1997).
CDKs and cyclins in transition(s).
  Curr Opin Genet Dev, 7, 32-38.  
9038181 R.Y.Poon, J.Lew, and T.Hunter (1997).
Identification of functional domains in the neuronal Cdk5 activator protein.
  J Biol Chem, 272, 5703-5708.  
9263984 S.J.Shankland (1997).
Cell-cycle control and renal disease.
  Kidney Int, 52, 294-308.  
9667861 S.S.Taylor, and E.Radzio-Andzelm (1997).
Protein kinase inhibition: natural and synthetic variations on a theme.
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  9334312 S.T.Wen, and R.A.Van Etten (1997).
The PAG gene product, a stress-induced protein with antioxidant properties, is an Abl SH3-binding protein and a physiological inhibitor of c-Abl tyrosine kinase activity.
  Genes Dev, 11, 2456-2467.  
9325318 S.W.Blain, E.Montalvo, and J.Massagué (1997).
Differential interaction of the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 with cyclin A-Cdk2 and cyclin D2-Cdk4.
  J Biol Chem, 272, 25863-25872.  
  17708934 T.Hunter, and R.Y.Poon (1997).
Cdc37: a protein kinase chaperone?
  Trends Cell Biol, 7, 157-161.  
8939669 D.O.Morgan (1996).
The dynamics of cyclin dependent kinase structure.
  Curr Opin Cell Biol, 8, 767-772.  
8861913 J.M.Gulbis, Z.Kelman, J.Hurwitz, M.O'Donnell, and J.Kuriyan (1996).
Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA.
  Cell, 87, 297-306.
PDB code: 1axc
8994876 L.N.Johnson, and M.O'Reilly (1996).
Control by phosphorylation.
  Curr Opin Struct Biol, 6, 762-769.  
  8943316 P.D.Adams, W.R.Sellers, S.K.Sharma, A.D.Wu, C.M.Nalin, and W.G.Kaelin (1996).
Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors.
  Mol Cell Biol, 16, 6623-6633.  
8876165 R.W.Kriwacki, L.Hengst, L.Tennant, S.I.Reed, and P.E.Wright (1996).
Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: conformational disorder mediates binding diversity.
  Proc Natl Acad Sci U S A, 93, 11504-11509.  
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.