Suppression of the p53- or pRB-mediated G1 checkpoint is required for E2F-induced S-phase entry.

TY - JOUR

T1 - Suppression of the p53- or pRB-mediated G1 checkpoint is required for E2F-induced S-phase entry.

AU - Lomazzi, Marina

AU - Moroni, M Cristina

AU - Jensen, Michael R

AU - Frittoli, Emanuela

AU - Helin, Kristian

N1 - Keywords: Animals; Cell Cycle Proteins; DNA-Binding Proteins; E2F Transcription Factors; E2F1 Transcription Factor; Fibroblasts; G1 Phase; Gene Expression Regulation; Humans; Mice; Retinoblastoma Protein; S Phase; Signal Transduction; Transcription Factors; Tumor Suppressor Protein p53

PY - 2002

Y1 - 2002

N2 - Deregulation of the retinoblastoma protein (pRB) pathway is a hallmark of cancer. In the absence of other genetic alterations, this deregulation results in lack of differentiation, hyperproliferation and apoptosis. The pRB protein acts as a transcriptional repressor by targeting the E2F transcription factors, whose functions are required for entry into S phase. Increased E2F activity can induce S phase in quiescent cells--this is a central element of most models for the development of cancer. We show that although E2F1 alone is not sufficient to induce S phase in diploid mouse and human fibroblasts, increased E2F1 activity can result in S-phase entry in diploid fibroblasts in which the p53-mediated G1 checkpoint is suppressed. In addition, we show that E2F1 can induce S phase in primary mouse fibroblasts lacking pRB. These results indicate that, in addition to acting as an E2F-dependent transcriptional repressor, pRB is also required for the cells to retain the G1 checkpoint in response to unprogrammed proliferative signals.

AB - Deregulation of the retinoblastoma protein (pRB) pathway is a hallmark of cancer. In the absence of other genetic alterations, this deregulation results in lack of differentiation, hyperproliferation and apoptosis. The pRB protein acts as a transcriptional repressor by targeting the E2F transcription factors, whose functions are required for entry into S phase. Increased E2F activity can induce S phase in quiescent cells--this is a central element of most models for the development of cancer. We show that although E2F1 alone is not sufficient to induce S phase in diploid mouse and human fibroblasts, increased E2F1 activity can result in S-phase entry in diploid fibroblasts in which the p53-mediated G1 checkpoint is suppressed. In addition, we show that E2F1 can induce S phase in primary mouse fibroblasts lacking pRB. These results indicate that, in addition to acting as an E2F-dependent transcriptional repressor, pRB is also required for the cells to retain the G1 checkpoint in response to unprogrammed proliferative signals.

U2 - 10.1038/ng891

DO - 10.1038/ng891

M3 - Journal article

C2 - 11992123

SN - 1061-4036

VL - 31

SP - 190

EP - 194

JO - Nature: New biology

JF - Nature: New biology

IS - 2

ER -