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* Residue conservation analysis
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Enzyme class:
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Chains A, B:
E.C.?
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DOI no:
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Mol Cell
22:731-740
(2006)
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PubMed id:
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Structure of the Tfb1/p53 complex: Insights into the interaction between the p62/Tfb1 subunit of TFIIH and the activation domain of p53.
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P.Di Lello,
L.M.Jenkins,
T.N.Jones,
B.D.Nguyen,
T.Hara,
H.Yamaguchi,
J.D.Dikeakos,
E.Appella,
P.Legault,
J.G.Omichinski.
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ABSTRACT
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The interaction between the amino-terminal transactivation domain (TAD) of p53
and TFIIH is directly correlated with the ability of p53 to activate both
transcription initiation and elongation. We have identified a region within the
p53 TAD that specifically interacts with the pleckstrin homology (PH) domain of
the p62 and Tfb1 subunits of human and yeast TFIIH. We have solved the 3D
structure of a complex between the p53 TAD and the PH domain of Tfb1 by NMR
spectroscopy. Our structure reveals that p53 forms a nine residue amphipathic
alpha helix (residues 47-55) upon binding to Tfb1. In addition, we demonstrate
that diphosphorylation of p53 at Ser46 and Thr55 leads to a significant
enhancement in p53 binding to p62 and Tfb1. These results indicate that a
phosphorylation cascade involving Ser46 and Thr55 of p53 could play an important
role in the regulation of select p53 target genes.
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Selected figure(s)
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Figure 3.
Figure 3. Structure of the Tfb1/p53 Complex
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Figure 4.
Figure 4. Structural Details of the Tfb1/p53 Interface
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2006,
22,
731-740)
copyright 2006.
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Figures were
selected
by the author.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.C.Joerger,
and
A.R.Fersht
(2010).
The tumor suppressor p53: from structures to drug discovery.
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Cold Spring Harb Perspect Biol,
2,
a000919.
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B.Xue,
A.K.Dunker,
and
V.N.Uversky
(2010).
Retro-MoRFs: Identifying Protein Binding Sites by Normal and Reverse Alignment and Intrinsic Disorder Prediction.
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Int J Mol Sci,
11,
3725-3747.
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C.W.Lee,
J.C.Ferreon,
A.C.Ferreon,
M.Arai,
and
P.E.Wright
(2010).
Graded enhancement of p53 binding to CREB-binding protein (CBP) by multisite phosphorylation.
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Proc Natl Acad Sci U S A,
107,
19290-19295.
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E.Herbig,
L.Warfield,
L.Fish,
J.Fishburn,
B.A.Knutson,
B.Moorefield,
D.Pacheco,
and
S.Hahn
(2010).
Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains.
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Mol Cell Biol,
30,
2376-2390.
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J.D.Amaral,
A.R.Correia,
C.J.Steer,
C.M.Gomes,
and
C.M.Rodrigues
(2010).
No evidence of direct binding between ursodeoxycholic acid and the p53 DNA-binding domain.
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Biosci Rep,
30,
359-364.
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J.Shlomai
(2010).
Redox control of protein-DNA interactions: from molecular mechanisms to significance in signal transduction, gene expression, and DNA replication.
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Antioxid Redox Signal,
13,
1429-1476.
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K.D.Meyer,
S.C.Lin,
C.Bernecky,
Y.Gao,
and
D.J.Taatjes
(2010).
p53 activates transcription by directing structural shifts in Mediator.
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Nat Struct Mol Biol,
17,
753-760.
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R.Puca,
L.Nardinocchi,
D.Givol,
and
G.D'Orazi
(2010).
Regulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells.
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Oncogene,
29,
4378-4387.
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S.Rajagopalan,
A.Andreeva,
T.J.Rutherford,
and
A.R.Fersht
(2010).
Mapping the physical and functional interactions between the tumor suppressors p53 and BRCA2.
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Proc Natl Acad Sci U S A,
107,
8587-8592.
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A.K.Sharma,
A.Ali,
R.Gogna,
A.K.Singh,
and
U.Pati
(2009).
p53 Amino-terminus region (1-125) stabilizes and restores heat denatured p53 wild phenotype.
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PLoS One,
4,
e7159.
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B.Mészáros,
I.Simon,
and
Z.Dosztányi
(2009).
Prediction of protein binding regions in disordered proteins.
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PLoS Comput Biol,
5,
e1000376.
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C.D.Trainor,
C.Mas,
P.Archambault,
P.Di Lello,
and
J.G.Omichinski
(2009).
GATA-1 associates with and inhibits p53.
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Blood,
114,
165-173.
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C.J.Tsai,
B.Ma,
and
R.Nussinov
(2009).
Protein-protein interaction networks: how can a hub protein bind so many different partners?
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Trends Biochem Sci,
34,
594-600.
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C.W.Lee,
M.Arai,
M.A.Martinez-Yamout,
H.J.Dyson,
and
P.E.Wright
(2009).
Mapping the interactions of the p53 transactivation domain with the KIX domain of CBP.
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Biochemistry,
48,
2115-2124.
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D.P.Teufel,
M.Bycroft,
and
A.R.Fersht
(2009).
Regulation by phosphorylation of the relative affinities of the N-terminal transactivation domains of p53 for p300 domains and Mdm2.
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Oncogene,
28,
2112-2118.
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D.W.Meek,
and
C.W.Anderson
(2009).
Posttranslational modification of p53: cooperative integrators of function.
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Cold Spring Harb Perspect Biol,
1,
a000950.
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H.Feng,
L.M.Jenkins,
S.R.Durell,
R.Hayashi,
S.J.Mazur,
S.Cherry,
J.E.Tropea,
M.Miller,
A.Wlodawer,
E.Appella,
and
Y.Bai
(2009).
Structural basis for p300 Taz2-p53 TAD1 binding and modulation by phosphorylation.
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Structure,
17,
202-210.
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PDB code:
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J.C.Ferreon,
C.W.Lee,
M.Arai,
M.A.Martinez-Yamout,
H.J.Dyson,
and
P.E.Wright
(2009).
Cooperative regulation of p53 by modulation of ternary complex formation with CBP/p300 and HDM2.
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Proc Natl Acad Sci U S A,
106,
6591-6596.
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L.M.Jenkins,
H.Yamaguchi,
R.Hayashi,
S.Cherry,
J.E.Tropea,
M.Miller,
A.Wlodawer,
E.Appella,
and
S.J.Mazur
(2009).
Two distinct motifs within the p53 transactivation domain bind to the Taz2 domain of p300 and are differentially affected by phosphorylation.
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Biochemistry,
48,
1244-1255.
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M.Miller,
Z.Dauter,
S.Cherry,
J.E.Tropea,
and
A.Wlodawer
(2009).
Structure of the Taz2 domain of p300: insights into ligand binding.
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Acta Crystallogr D Biol Crystallogr,
65,
1301-1308.
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PDB code:
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T.S.Wong,
S.Rajagopalan,
F.M.Townsley,
S.M.Freund,
M.Petrovich,
D.Loakes,
and
A.R.Fersht
(2009).
Physical and functional interactions between human mitochondrial single-stranded DNA-binding protein and tumour suppressor p53.
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Nucleic Acids Res,
37,
568-581.
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A.C.Joerger,
and
A.R.Fersht
(2008).
Structural biology of the tumor suppressor p53.
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Annu Rev Biochem,
77,
557-582.
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A.M.Gamper,
and
R.G.Roeder
(2008).
Multivalent binding of p53 to the STAGA complex mediates coactivator recruitment after UV damage.
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Mol Cell Biol,
28,
2517-2527.
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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.
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BMC Genomics,
9,
S1.
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J.B.Thoden,
L.A.Ryan,
R.J.Reece,
and
H.M.Holden
(2008).
The Interaction between an Acidic Transcriptional Activator and Its Inhibitor: THE MOLECULAR BASIS OF Gal4p RECOGNITION BY Gal80p.
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J Biol Chem,
283,
30266-30272.
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PDB code:
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L.M.Jenkins,
S.J.Mazur,
M.Rossi,
O.Gaidarenko,
Y.Xu,
and
E.Appella
(2008).
Quantitative proteomics analysis of the effects of ionizing radiation in wild type and p53 K317R knock-in mouse thymocytes.
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Mol Cell Proteomics,
7,
716-727.
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M.Okuda,
A.Tanaka,
M.Satoh,
S.Mizuta,
M.Takazawa,
Y.Ohkuma,
and
Y.Nishimura
(2008).
Structural insight into the TFIIE-TFIIH interaction: TFIIE and p53 share the binding region on TFIIH.
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EMBO J,
27,
1161-1171.
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PDB codes:
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M.Rossi,
O.N.Demidov,
C.W.Anderson,
E.Appella,
and
S.J.Mazur
(2008).
Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites.
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Nucleic Acids Res,
36,
7168-7180.
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O.Okhrimenko,
and
I.Jelesarov
(2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
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J Mol Recognit,
21,
1.
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P.Di Lello,
L.M.Miller Jenkins,
C.Mas,
C.Langlois,
E.Malitskaya,
A.Fradet-Turcotte,
J.Archambault,
P.Legault,
and
J.G.Omichinski
(2008).
p53 and TFIIEalpha share a common binding site on the Tfb1/p62 subunit of TFIIH.
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Proc Natl Acad Sci U S A,
105,
106-111.
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PDB code:
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S.K.Balakrishnan,
and
D.S.Gross
(2008).
The tumor suppressor p53 associates with gene coding regions and co-traverses with elongating RNA polymerase II in an in vivo model.
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Oncogene,
27,
2661-2672.
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Y.Li,
T.Ozaki,
H.Kikuchi,
H.Yamamoto,
M.Ohira,
and
A.Nakagawara
(2008).
A novel HECT-type E3 ubiquitin protein ligase NEDL1 enhances the p53-mediated apoptotic cell death in its catalytic activity-independent manner.
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Oncogene,
27,
3700-3709.
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D.P.Teufel,
S.M.Freund,
M.Bycroft,
and
A.R.Fersht
(2007).
Four domains of p300 each bind tightly to a sequence spanning both transactivation subdomains of p53.
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Proc Natl Acad Sci U S A,
104,
7009-7014.
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S.W.Chi,
D.H.Kim,
S.H.Lee,
I.Chang,
and
K.H.Han
(2007).
Pre-structured motifs in the natively unstructured preS1 surface antigen of hepatitis B virus.
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Protein Sci,
16,
2108-2117.
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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
code is
shown on the right.
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Links
