Apoptosis-stimulating protein of p53-2 (ASPP2/53BP2L) is an E2F target gene

D. Chen, E. Padiernos, F. Ding, Izidore Lossos, C. D. Lopez

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The p53 pathway is a central apoptotic regulator. Deregulation of the Rb/E2F pathway occurs in a majority of tumors, resulting in both unrestrained proliferation and enhanced apoptosis sensitivity via p53-dependent and independent mechanisms. However, the mechanisms coupling the p53 and Rb/E2F pathways remain incompletely understood. We report that ASPP2/53BP2L, a p53/p73-binding protein that promotes p53/p73-dependent apoptosis, is an E2F target gene. The ASPP2/53BP2L promoter was identified and ectopic expression of transcription-competent E2F-1 (E2F-2 and E2F-3) stimulated an ASPP2/53BP2L promoter-luciferase reporter. Mutational analysis of the ASPP2/53BP2L promoter identified E2F-binding sites that cooperate for E2F-1 induction and basal repression of ASPP2/53BP2L. Moreover, endogenous ASPP2/53BP2L levels increased after E2F-1 expression, and E2F-1 bound the endogenous ASPP2/53BP2L promoter after chromatin immunoprecipitation. Typical for an E2F target, ASPP2/53BP2L expression was maximal in early S-phase. Thus, ASPP2/53BP2L is downstream of E2F, suggesting that it functions as a common link between the p53/p73 and Rb/E2F apoptotic pathways.

Original languageEnglish
Pages (from-to)358-368
Number of pages11
JournalCell Death and Differentiation
Volume12
Issue number4
DOIs
StatePublished - Apr 1 2005

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Apoptosis
Chromatin Immunoprecipitation
Luciferases
S Phase
Genes
Carrier Proteins
Proteins
Binding Sites
Neoplasms
Ectopic Gene Expression
Tumor Protein p73

Keywords

  • 53BP2
  • Apoptosis
  • ASPP2
  • E2F
  • p53

ASJC Scopus subject areas

  • Cell Biology

Cite this

Apoptosis-stimulating protein of p53-2 (ASPP2/53BP2L) is an E2F target gene. / Chen, D.; Padiernos, E.; Ding, F.; Lossos, Izidore; Lopez, C. D.

In: Cell Death and Differentiation, Vol. 12, No. 4, 01.04.2005, p. 358-368.

Research output: Contribution to journalArticle

Chen, D. ; Padiernos, E. ; Ding, F. ; Lossos, Izidore ; Lopez, C. D. / Apoptosis-stimulating protein of p53-2 (ASPP2/53BP2L) is an E2F target gene. In: Cell Death and Differentiation. 2005 ; Vol. 12, No. 4. pp. 358-368.
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