The pRB-related protein p107 contains two growth suppression domains: Independent interactions with E2F and cyclin/cdk complexes

L. Zhu, G. Enders, J. A. Lees, R. L. Beijersbergen, R. Bernards, E. Harlow

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

Unregulated expression of either the retinoblastoma protein (pRB) or the related protein p107 can cause growth arrest of sensitive cells in the G1 phase of the cell cycle. However, growth arrests mediated by p107 and pRB are not identical. Through structure-function and co-expression analyses we have dissected the p107 molecule into two domains that independently are able to block cell cycle progression. One domain corresponds to the sequences needed for interaction with the transcription factor E2F, and the other corresponds to the interaction domain for cyclin A or cyclin E complexes. In cervical carcinoma cell line C33A, which was previously shown to be sensitive to p107 but resistant to pRB growth suppression, only the cyclin binding domain is active as a growth suppressor. Furthermore, we show that these two independent domains are functional in untransformed mouse fibroblasts. Together, these results provide experimental evidence for the presence of two functional domains in p107 and pinpoint an important functional difference between p107 and pRB.

Original languageEnglish (US)
Pages (from-to)1904-1913
Number of pages10
JournalEMBO Journal
Volume14
Issue number9
StatePublished - Jan 1 1995
Externally publishedYes

Keywords

  • Cell cycle
  • Functional domains
  • Growth suppression
  • p107

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Zhu, L., Enders, G., Lees, J. A., Beijersbergen, R. L., Bernards, R., & Harlow, E. (1995). The pRB-related protein p107 contains two growth suppression domains: Independent interactions with E2F and cyclin/cdk complexes. EMBO Journal, 14(9), 1904-1913.