The pRB-related protein p107 contains two growth suppression domains

Independent interactions with E2F and cyclin/cdk complexes

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

Research output: Contribution to journalArticle

127 Citations (Scopus)

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 - 1995
Externally publishedYes

Fingerprint

Cyclins
Cells
Growth
Cell Cycle
Proteins
E2F Transcription Factors
Cyclin A
Cyclin E
Retinoblastoma Protein
G1 Phase
Fibroblasts
Carcinoma
Cell Line
Molecules

Keywords

  • Cell cycle
  • Functional domains
  • Growth suppression
  • p107

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

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.

The pRB-related protein p107 contains two growth suppression domains : Independent interactions with E2F and cyclin/cdk complexes. / Zhu, Liang; Enders, G.; Lees, J. A.; Beijersbergen, R. L.; Bernards, R.; Harlow, E.

In: EMBO Journal, Vol. 14, No. 9, 1995, p. 1904-1913.

Research output: Contribution to journalArticle

Zhu, L, Enders, G, Lees, JA, Beijersbergen, RL, 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, vol. 14, no. 9, pp. 1904-1913.
Zhu, Liang ; Enders, G. ; Lees, J. A. ; Beijersbergen, R. L. ; Bernards, R. ; Harlow, E. / The pRB-related protein p107 contains two growth suppression domains : Independent interactions with E2F and cyclin/cdk complexes. In: EMBO Journal. 1995 ; Vol. 14, No. 9. pp. 1904-1913.
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