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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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

D Chen1, E Padiernos, F Ding

  • 1Department of Medicine, Division of Hematology and Medical Oncology, L586B, Oregon Health & Science University, Portland, OR 97239, USA.

Cell Death and Differentiation
|December 14, 2004
PubMed

Insights

The ASPP2/53BP2L gene, a regulator of apoptosis, is controlled by the Rb/E2F pathway. This discovery reveals ASPP2/53BP2L as a crucial link connecting the p53 and Rb/E2F apoptotic signaling pathways in cancer.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Signaling

Background:

  • The p53 pathway is a key regulator of apoptosis.
  • The Rb/E2F pathway is frequently deregulated in cancer, impacting proliferation and apoptosis.
  • The precise mechanisms linking p53 and Rb/E2F pathways are not fully understood.

Purpose of the Study:

  • To investigate the relationship between the p53 and Rb/E2F apoptotic pathways.
  • To identify novel targets of the Rb/E2F pathway involved in apoptosis regulation.
  • To elucidate the role of ASPP2/53BP2L in the context of these signaling networks.

Main Methods:

  • Promoter-luciferase reporter assays to identify E2F-responsive elements.
  • Mutational analysis of the ASPP2/53BP2L promoter.
  • Chromatin immunoprecipitation (ChIP) to assess E2F binding to the ASPP2/53BP2L promoter.
  • Analysis of endogenous ASPP2/53BP2L expression in relation to E2F-1 levels and cell cycle phase.

Main Results:

  • ASPP2/53BP2L was identified as a direct E2F target gene.
  • Ectopic E2F-1, E2F-2, and E2F-3 expression upregulated the ASPP2/53BP2L promoter activity.
  • Mutational analysis revealed functional E2F-binding sites in the ASPP2/53BP2L promoter.
  • Endogenous ASPP2/53BP2L levels increased upon E2F-1 expression, with E2F-1 binding to the promoter.
  • ASPP2/53BP2L expression peaked in early S-phase, characteristic of E2F targets.

Conclusions:

  • ASPP2/53BP2L is a downstream target gene regulated by the Rb/E2F pathway.
  • ASPP2/53BP2L acts as a molecular bridge connecting the p53/p73 and Rb/E2F apoptotic pathways.
  • This finding provides new insights into the coordinated regulation of apoptosis in cancer.

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