期刊
CELL CYCLE
卷 8, 期 14, 页码 2146-2151出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.8.14.9089
关键词
LSF; cyclin C/CDK; ERK; thymidylate synthetase; E2F; pRb; p53; G(1) phase; S phase; restriction point
类别
资金
- [CA-081157]
Cell cycle progression in mammalian cells from G(1) into S phase requires sensing and integration of multiple inputs, in order to determine whether to continue to cellular DNA replication and subsequently, to cell division. Passage to S requires transition through the restriction point, which at a molecular level consists of a bistable switch involving E2Fs and pRb family members. At the G(1)/S boundary, a number of genes essential for DNA replication and cell cycle progression are upregulated, promoting entry into S phase. Although the activating E2Fs are the most extensively characterized transcription factors driving G(1)/S expression, LSF is also a transcription factor essential for stimulating G(1)/S gene expression. A critical LSF target gene at this stage, Tyms, encodes thymidylate synthetase. In investigating how LSF is activated in a cell cycle-dependent manner, we recently identified a novel time delay mechanism for regulating its activity during G1 progression, which is apparently independent of the E2F/pRb axis. This involves inhibition of LSF in early G(1) by two major proliferative signaling pathways: ERK and cyclin C/CDK, followed by gradual dephosphorylation during mid-to late-G(1). Whether LSF and E2F act independently or in concert to promote G(1)/S progression remains to be determined.
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