Apaf-1 is a transcriptional target for E2F and p53

M. Cristina Moroni, Emma S. Hickman, Eros Lazzerini Denchi, Greta Caprara, Elena Colli, Francesco Cecconi, Heiko Müller, Kristian Helin

Research output: Contribution to journalArticle

Abstract

Loss of function of the retinoblastoma protein, pRB, leads to lack of differentiation, hyperproliferation and apoptosis. Inactivation of pRB results in deregulated E2F activity, which in turn induces entry to S-phase and apoptosis. Induction of apoptosis by either the loss of pRB or the deregulation of E2F activity occurs via both p53-dependent and p53-independent mechanisms. The mechanism by which E2F induces apoptosis is still unclear. Here we show that E2F1 directly regulates the expression of Apaf-1, the gene for apoptosis protease-activating factor 1. These results provide a direct link between the deregulation of the pRB pathway and apoptosis. Furthermore, because the pRB pathway is functionally inactivated in most cancers, the identification of Apaf-1 as a transcriptional target for E2F might explain the increased sensitivity of tumour cells to chemotherapy. We also show that, independently of the pRB pathway, Apaf-1 is a direct transcriptional target of p53, suggesting that p53 might sensitize cells to apoptosis by increasing Apaf-1 levels.

Original languageEnglish
Pages (from-to)552-558
Number of pages7
JournalNature Cell Biology
Volume3
Issue number6
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Cell Biology

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    Moroni, M. C., Hickman, E. S., Denchi, E. L., Caprara, G., Colli, E., Cecconi, F., Müller, H., & Helin, K. (2001). Apaf-1 is a transcriptional target for E2F and p53. Nature Cell Biology, 3(6), 552-558. https://doi.org/10.1038/35078527