Transcription factors LSF and E2Fs: tandem cyclists driving G0 to S?
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 G(1) 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.
Hansen
Ulla
U
Department of Biology and Program in Molecular Biology, Cell Biology and Biochemistry, Boston University, Boston, MA 02215, USA. uhansen@bu.edu
Owens
Laura
L
Saxena
Utsav H
UH
D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D050684:E2F Transcription Factors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C501906:TFCP2 protein, human; D014157:Transcription Factors; D018844:Cyclin-Dependent Kinases; D048049:Extracellular Signal-Regulated MAP Kinases