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PMID: 10611293 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

The alpha-helical FXXPhiPhi motif in p53: TAF interaction and discrimination by MDM2.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 26 ·1999-12-21 ·Pages 14801-6

Uesugi M, Verdine GL

Abstract

Transcriptional activation domains share little sequence homology and generally lack folded structures in the absence of their targets, aspects that have rendered activation domains difficult to characterize. Here, a combination of biochemical and nuclear magnetic resonance experiments demonstrates that the activation domain of the tumor suppressor p53 has an FXXPhiPhi motif (F, Phe; X, any amino acids; Phi, hydrophobic residues) that folds into an alpha-helix upon binding to one of its targets, hTAF(II)31 (a human TFIID TATA box-binding protein-associated factor). MDM2, the cellular attenuator of p53, discriminates the FXXPhiPhi motif of p53 from those of NF-kappaB p65 and VP16 and specifically inhibits p53 activity. Our studies support the notion that the FXXPhiPhi sequence is a general alpha-helical recognition motif for hTAF(II)31 and provide insights into the mechanistic basis for regulation of p53 function.

MeSH Terms
Amino Acid Motifs Amino Acid Sequence Humans Molecular Sequence Data Nuclear Proteins Protein Binding Protein Structure, Secondary Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-mdm2 TATA-Binding Protein Associated Factors Trans-Activators/metabolism Transcription Factor TFIID Transcriptional Activation Tumor Suppressor Protein p53/chemistry,metabolism
Chemicals
Nuclear Proteins Proto-Oncogene Proteins TAF9 protein, human TATA-Binding Protein Associated Factors Trans-Activators Transcription Factor TFIID Tumor Suppressor Protein p53 MDM2 protein, human Proto-Oncogene Proteins c-mdm2
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Uesugi M
Department of Chemistry, Harvard University, Cambridge, MA 02138, USA.
Verdine G L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.26.14801
Published
1999-12-21
Pages
14801-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24728
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.96.26.14801 PMC Full Text View journal details
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