Regulation in S phase by E2F.
The DNA synthetic S phase of the unperturbed cell cycle is a closed system, as compared to regulation of G(1) by external growth factors. The E2F family provides internal control in S phase by transcribing genes required for deoxynucleotide triphosphate (dNTP) and DNA synthesis. Furthermore, over expression of E2F-1 activates programmed cell death (apoptosis), a safeguarding signal of aberrant growth of cells that have become carcinogenic. Mechanisms for control of E2F-1 are thus essential. The hypothesis is proposed that deoxythymidine triphosphate (dTTP) allosterically feedback controls E2F-1 to regulate both DNA synthesis and apoptosis. This may act either upon production of E2F-1 or its degradation.
Dana Farber Cancer Institute, Boston, Massachusetts, USA. arthur_pardee@dfci.harvard.edu
Arthur B
AB
Pardee
Chiang J
CJ
Li
G Prem Veer
GP
Reddy
D000494:Allosteric Regulation / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics*; D004247:DNA / Q000096:biosynthesis*; D050684:E2F Transcription Factors / Q000235:genetics*; D025461:Feedback, Physiological / Q000502:physiology; D006801:Humans; D016196:S Phase / Q000235:genetics*; D013942:Thymine Nucleotides / Q000378:metabolism*
D018797:Cell Cycle Proteins; D050684:E2F Transcription Factors; D013942:Thymine Nucleotides; D004247:DNA; C024157:thymidine 5'-triphosphate