The domain of p53 required for binding HPV 16 E6 is separable from the degradation domain

C. P. Mansur, B. Marcus, S. Dalal, Elliot Androphy

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The E6 proteins of specific cancer-associated human papillomaviruses (HPVs) complex with and mediate degradation of the cellular anti-oncogene p53 in vitro. A critical property of p53 is its ability to stimulate transcription from promoters containing its recognition sequence. HPV E6, mutant p53 proteins, and several DNA tumor virus oncogenes inhibit the transcriptional activity of wild-type p53. In this report, the structural requirements for the interaction between HPV 16 E6 and p53 were examined both in vivo and in vitro. p53-stimulated transcription was efficiently inhibited by wild-type HPV 16 E6 and E6 mutants competent for p53 binding and degradation. A series of p53 deletions and hybrid proteins with heterologous DNA binding, dimerization and transactivation domains were analysed for transcriptional interaction with HPV 16 E6 to determine the domains of p53 required for transcriptional inhibition. These chimeric proteins were also analysed for E6 binding and E6-mediated degradation in vitro. In both assays, complex formation with E6 was mediated through the amino-terminal 345 amino acids of p53 without a specific requirement for its C-terminus. Hybrid proteins containing residues 161-345 of p53 also bound E6, but this segment of p53 was not susceptible to E6 induced proteolysis. A second region of p53, within its N-terminal 160 aa, is required for E6 and p53 is not mediated through the C-terminus of p53 and that binding and degradation are separable.

Original languageEnglish (US)
Pages (from-to)457-465
Number of pages9
JournalOncogene
Volume10
Issue number3
StatePublished - 1995
Externally publishedYes

Fingerprint

Human papillomavirus 16
Proteins
DNA Tumor Viruses
Dimerization
Mutant Proteins
Tumor Suppressor Genes
Oncogenes
Transcriptional Activation
Proteolysis
Amino Acids
DNA
In Vitro Techniques
Neoplasms

Keywords

  • p53
  • Papillomavirus E6 protein
  • Transcriptional activation

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

The domain of p53 required for binding HPV 16 E6 is separable from the degradation domain. / Mansur, C. P.; Marcus, B.; Dalal, S.; Androphy, Elliot.

In: Oncogene, Vol. 10, No. 3, 1995, p. 457-465.

Research output: Contribution to journalArticle

Mansur, C. P. ; Marcus, B. ; Dalal, S. ; Androphy, Elliot. / The domain of p53 required for binding HPV 16 E6 is separable from the degradation domain. In: Oncogene. 1995 ; Vol. 10, No. 3. pp. 457-465.
@article{94277569316747bea5a2e0b44a724154,
title = "The domain of p53 required for binding HPV 16 E6 is separable from the degradation domain",
abstract = "The E6 proteins of specific cancer-associated human papillomaviruses (HPVs) complex with and mediate degradation of the cellular anti-oncogene p53 in vitro. A critical property of p53 is its ability to stimulate transcription from promoters containing its recognition sequence. HPV E6, mutant p53 proteins, and several DNA tumor virus oncogenes inhibit the transcriptional activity of wild-type p53. In this report, the structural requirements for the interaction between HPV 16 E6 and p53 were examined both in vivo and in vitro. p53-stimulated transcription was efficiently inhibited by wild-type HPV 16 E6 and E6 mutants competent for p53 binding and degradation. A series of p53 deletions and hybrid proteins with heterologous DNA binding, dimerization and transactivation domains were analysed for transcriptional interaction with HPV 16 E6 to determine the domains of p53 required for transcriptional inhibition. These chimeric proteins were also analysed for E6 binding and E6-mediated degradation in vitro. In both assays, complex formation with E6 was mediated through the amino-terminal 345 amino acids of p53 without a specific requirement for its C-terminus. Hybrid proteins containing residues 161-345 of p53 also bound E6, but this segment of p53 was not susceptible to E6 induced proteolysis. A second region of p53, within its N-terminal 160 aa, is required for E6 and p53 is not mediated through the C-terminus of p53 and that binding and degradation are separable.",
keywords = "p53, Papillomavirus E6 protein, Transcriptional activation",
author = "Mansur, {C. P.} and B. Marcus and S. Dalal and Elliot Androphy",
year = "1995",
language = "English (US)",
volume = "10",
pages = "457--465",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - The domain of p53 required for binding HPV 16 E6 is separable from the degradation domain

AU - Mansur, C. P.

AU - Marcus, B.

AU - Dalal, S.

AU - Androphy, Elliot

PY - 1995

Y1 - 1995

N2 - The E6 proteins of specific cancer-associated human papillomaviruses (HPVs) complex with and mediate degradation of the cellular anti-oncogene p53 in vitro. A critical property of p53 is its ability to stimulate transcription from promoters containing its recognition sequence. HPV E6, mutant p53 proteins, and several DNA tumor virus oncogenes inhibit the transcriptional activity of wild-type p53. In this report, the structural requirements for the interaction between HPV 16 E6 and p53 were examined both in vivo and in vitro. p53-stimulated transcription was efficiently inhibited by wild-type HPV 16 E6 and E6 mutants competent for p53 binding and degradation. A series of p53 deletions and hybrid proteins with heterologous DNA binding, dimerization and transactivation domains were analysed for transcriptional interaction with HPV 16 E6 to determine the domains of p53 required for transcriptional inhibition. These chimeric proteins were also analysed for E6 binding and E6-mediated degradation in vitro. In both assays, complex formation with E6 was mediated through the amino-terminal 345 amino acids of p53 without a specific requirement for its C-terminus. Hybrid proteins containing residues 161-345 of p53 also bound E6, but this segment of p53 was not susceptible to E6 induced proteolysis. A second region of p53, within its N-terminal 160 aa, is required for E6 and p53 is not mediated through the C-terminus of p53 and that binding and degradation are separable.

AB - The E6 proteins of specific cancer-associated human papillomaviruses (HPVs) complex with and mediate degradation of the cellular anti-oncogene p53 in vitro. A critical property of p53 is its ability to stimulate transcription from promoters containing its recognition sequence. HPV E6, mutant p53 proteins, and several DNA tumor virus oncogenes inhibit the transcriptional activity of wild-type p53. In this report, the structural requirements for the interaction between HPV 16 E6 and p53 were examined both in vivo and in vitro. p53-stimulated transcription was efficiently inhibited by wild-type HPV 16 E6 and E6 mutants competent for p53 binding and degradation. A series of p53 deletions and hybrid proteins with heterologous DNA binding, dimerization and transactivation domains were analysed for transcriptional interaction with HPV 16 E6 to determine the domains of p53 required for transcriptional inhibition. These chimeric proteins were also analysed for E6 binding and E6-mediated degradation in vitro. In both assays, complex formation with E6 was mediated through the amino-terminal 345 amino acids of p53 without a specific requirement for its C-terminus. Hybrid proteins containing residues 161-345 of p53 also bound E6, but this segment of p53 was not susceptible to E6 induced proteolysis. A second region of p53, within its N-terminal 160 aa, is required for E6 and p53 is not mediated through the C-terminus of p53 and that binding and degradation are separable.

KW - p53

KW - Papillomavirus E6 protein

KW - Transcriptional activation

UR - http://www.scopus.com/inward/record.url?scp=0028821580&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028821580&partnerID=8YFLogxK

M3 - Article

VL - 10

SP - 457

EP - 465

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 3

ER -