Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 190-194 |
| Number of pages | 5 |
| Journal | Nature Genetics |
| Volume | 31 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jun 2002 |
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ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Suppression of the p53- or pRB-mediated G1 checkpoint is required for E2F-induced S-phase entry. / Lomazzi, Marina; Moroni, M. Cristina; Jensen, Michael R.; Frittoli, Emanuela; Helin, Kristian.
In: Nature Genetics, Vol. 31, No. 2, 06.2002, p. 190-194.Research output: Contribution to journal › Article
}
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
PY - 2002/6
Y1 - 2002/6
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.
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U2 - 10.1038/ng891
DO - 10.1038/ng891
M3 - Article
VL - 31
SP - 190
EP - 194
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 2
ER -