Inhibition of cell proliferation by p 107, a relative of the retinoblastoma protein

Liang Zhu, Sander Den Van Heuvel, Kristian Helin, Ali Fattaey, Mark Ewen, David Livingston, Nicholas Dyson, Ed Harlow

Research output: Contribution to journalArticle

436 Citations (Scopus)

Abstract

The cellular protein p107 shares many structural and biochemical features with the retinoblastoma gene product, pRB. We have isolated a full-length cDNA for human p107 and have used this clone to study the function of p107. We show that, like pRB, p107 is a potent inhibitor of E2F-mediated trans-activation, and overexpression of p107 can inhibit proliferation in certain cell types, arresting sensitive cells in G1. Several experiments, however, showed that growth inhibition by pRB and p107 did not occur through the same mechanism. First, in the cervical carcinoma cell line C33A, p107 was able to block cell proliferation, whereas pRB could not, even though both proteins were potent inhibitors of E2F-mediated transcription in this cell line. Second, growth arrest by pRB and p107 was rescued differentially by various cell cycle regulators. Third, some mutants of p107 that cannot associate with adenovirus E1A were still able to inhibit cell proliferation, whereas analogous mutants in pRB are known to be unable to block cell growth. Together, these results suggest a biological role of p107 that is related, but not identical, to that of pRB.

Original languageEnglish (US)
Pages (from-to)1111-1125
Number of pages15
JournalGenes and Development
Volume7
Issue number7
StatePublished - 1993
Externally publishedYes

Fingerprint

Retinoblastoma Protein
Cell Proliferation
Growth
Retinoblastoma Genes
Cell Line
Adenoviridae
Cell Cycle
Proteins
Complementary DNA
Clone Cells
Carcinoma

Keywords

  • E1A
  • E2F
  • Growth suppression
  • P107
  • PRB

ASJC Scopus subject areas

  • Developmental Biology
  • Genetics

Cite this

Zhu, L., Van Heuvel, S. D., Helin, K., Fattaey, A., Ewen, M., Livingston, D., ... Harlow, E. (1993). Inhibition of cell proliferation by p 107, a relative of the retinoblastoma protein. Genes and Development, 7(7), 1111-1125.

Inhibition of cell proliferation by p 107, a relative of the retinoblastoma protein. / Zhu, Liang; Van Heuvel, Sander Den; Helin, Kristian; Fattaey, Ali; Ewen, Mark; Livingston, David; Dyson, Nicholas; Harlow, Ed.

In: Genes and Development, Vol. 7, No. 7, 1993, p. 1111-1125.

Research output: Contribution to journalArticle

Zhu, L, Van Heuvel, SD, Helin, K, Fattaey, A, Ewen, M, Livingston, D, Dyson, N & Harlow, E 1993, 'Inhibition of cell proliferation by p 107, a relative of the retinoblastoma protein', Genes and Development, vol. 7, no. 7, pp. 1111-1125.
Zhu L, Van Heuvel SD, Helin K, Fattaey A, Ewen M, Livingston D et al. Inhibition of cell proliferation by p 107, a relative of the retinoblastoma protein. Genes and Development. 1993;7(7):1111-1125.
Zhu, Liang ; Van Heuvel, Sander Den ; Helin, Kristian ; Fattaey, Ali ; Ewen, Mark ; Livingston, David ; Dyson, Nicholas ; Harlow, Ed. / Inhibition of cell proliferation by p 107, a relative of the retinoblastoma protein. In: Genes and Development. 1993 ; Vol. 7, No. 7. pp. 1111-1125.
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