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PMID: 8612585 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Functional interactions between p53 and the TFIIH complex are affected by tumour-associated mutations.

The EMBO journal ·Vol. 15 ·No. 7 ·1996-04-01 ·Pages 1615-24

Léveillard T, Andera L, Bissonnette N, Schaeffer L, Bracco L, Egly JM, Wasylyk B

Abstract

The p53 tumour suppressor is mutated in the majority of human tumours. p53's proposed role as the guardian of the genome is reflected in its multiple effects on transcription genome stability, cell growth and survival. We show that p53 interacts both physically and functionally with the TFIIH complex. There are multiple protein-protein contacts, involving two regions of p53 and three subunits of TFIIH, ERCC2 (XPD), ERCC3 (XPB) and p62. p53 and its C-terminus (amino acids 320-393) inhibit both of the TFIIH helicases and in vitro transcription in the absence of TFIIH. Transcription inhibition is overcome by TFIIH. The N-terminal region of p53 (1-320), lacking the C-terminus, is inactive on its own, yet apparently affects the activity of the C-terminus in the native protein. Interestingly, mutant p53s that are frequently found in tumours are less efficient inhibitors of the helicases and transcription. We hypothesize that the interactions provide an immediate and direct link for p53 to the multiple functions of TFIIH in transcription, DNA repair and possibly the cell cycle.

MeSH Terms
Animals Binding Sites/genetics Cell Cycle DNA Helicases/antagonists & inhibitors,metabolism DNA Repair/genetics,physiology DNA-Binding Proteins Enzyme Inhibitors/metabolism Humans In Vitro Techniques Mutation Neoplasms/genetics,metabolism Protein Binding Proteins/genetics,metabolism Recombinant Proteins/genetics,metabolism Transcription Factor TFIIH Transcription Factors/antagonists & inhibitors,metabolism Transcription Factors, TFII Transcription, Genetic Tumor Suppressor Protein p53/genetics,metabolism Xeroderma Pigmentosum Group D Protein
Chemicals
DNA-Binding Proteins Enzyme Inhibitors Proteins Recombinant Proteins Transcription Factors Transcription Factors, TFII Tumor Suppressor Protein p53 Transcription Factor TFIIH DNA Helicases Xeroderma Pigmentosum Group D Protein ERCC2 protein, human
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Léveillard T
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Andera L
Bissonnette N
Schaeffer L
Bracco L
Egly J M
Wasylyk B
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-04-01
Pages
1615-24
Language
English
Region
England
NLM ID
8208664
PMCID
PMC450071
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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