TY - JOUR

T1 - Apaf-1 is a transcriptional target for E2F and p53.

AU - Moroni, M C

AU - Hickman, E S

AU - Lazzerini Denchi, E

AU - Caprara, G

AU - Colli, E

AU - Cecconi, F

AU - Müller, H

AU - Helin, K

N1 - Keywords: Animals; Apoptotic Protease-Activating Factor 1; Cell Cycle Proteins; DNA-Binding Proteins; E2F Transcription Factors; E2F1 Transcription Factor; Embryo, Mammalian; Humans; Mice; Promoter Regions (Genetics); Proteins; Retinoblastoma Protein; Trans-Activation (Genetics); Transcription Factors; Transcription, Genetic; Tumor Suppressor Protein p53

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

U2 - 10.1038/35078527

DO - 10.1038/35078527

M3 - Journal article

C2 - 11389439

VL - 3

SP - 552

EP - 558

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 6

ER -