Human E2F-1 Reactivates Cell Cycle Progression in Ventricular Myocytes and Represses Cardiac Gene Transcription

Dev Biol. 1996 Nov 1;179(2):402-11. doi: 10.1006/dbio.1996.0270.

Abstract

The "pocket" protein- and p300-binding domains of E1A mediate alternative pathways that, independently, provoke S phase reentry in ventricular muscle cells and repress cardiac-specific transcription. In the present study, we utilized recombinant adenovirus to deliver mammalian E2F-1, whose release from pocket proteins may underlie effects of E1A and mitogenic signaling. Like E1A, E2F-1 proved cytotoxic in the absence of E1B. Used along with E1B to avert apoptosis, E2F-1 inhibited the cardiac and skeletal alpha-actin promoters, serum response factor abundance, and sarcomeric actin biosynthesis, while inducing DNA synthesis and proliferating cell nuclear antigen. Image analysis of Feulgen-stained nuclei corroborated a parallel increase in DNA content, with accumulation in G2/M. Thus, E2F-1 suffices for all observed actions of E1A in cardiac myocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins*
  • Cell Cycle / genetics*
  • Cell Cycle Proteins*
  • Cells, Cultured
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Gene Expression Regulation*
  • Gene Transfer Techniques
  • Heart Ventricles*
  • Humans
  • Rats
  • Rats, Sprague-Dawley
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors / genetics*
  • Transcription, Genetic / genetics*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2f1 protein, rat
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors