A complex between E2F and the pRb-related protein p 130 is specifically targeted by the simian virus 40 large T antigen during cell transformation

Dieter A. Wolf, Heiko Hermeking, Thomas Albert, Thomas Herzinger, Peter Kind, Dirk Eick

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The p130 protein is a recently cloned member of the retinoblastoma protein family. We show here that transformation of NIH3T3-L1 fibroblasts (L1 cells) by the simian virus 40 large T antigen (LTAg) depends on the disruption of DNA binding complexes between transcription factor E2F and p130. LTAg binds to the pocket region of p130 in vivo and disrupts the E2F-p130 complexes. E2F-p130 complexes are present only in quiescent L1 cells and disappear at the G1/S phase boundary concomitantly to induction of DNA synthesis and expression of the E2F-regulated cdc2 gene, p130 is a substrate of cyclin-dependent kinase 2 (Cdk2) in vitro and associates with a Cdk in vivo which is activated upon serum stimulation in late G1. Overexpression of p130 inhibits cdc2 promoter activity and entry of quiescent L1 cells into S phase. The results demonstrate that p130 is a negative regulator of cell cycle progression which is specifically targeted by LTAg during cell transformation.

Original languageEnglish
Pages (from-to)2067-2078
Number of pages12
JournalOncogene
Volume10
Issue number11
StatePublished - 1 Jun 1995
Externally publishedYes

Keywords

  • Cell cycle
  • E2F
  • SV40 large T antigen
  • Transformation
  • p130

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