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Regulation of cyclin E transcription by E2Fs and retinoblastoma protein.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Cyclin E is critical for the advance of cells through the G1 phase of their growth cycle. Transcription of the cyclin E gene is known to be cell cycle-dependent. We have shown previously that mRNA levels of cyclin E are regulated positively by mitogens and negatively by TGF-beta. Much circumstantial evidence implicates both E2F transcription factors and the retinoblastoma protein (pRB) in the control of cyclin E expression. However, the molecular basis of this control has remained unclear. We report here the cloning of the cyclin E promoter and the identification of several putative E2F binding sites within the promoter sequence. We have found that cell cycle regulation of cyclin E transcription is mediated by E2F binding sites present in the promoter. The activity of this promoter can be regulated negatively by pRB. Our results suggest the operation of a positive-feedback loop in late G1 that functions to ensure continued cyclin E expression and pRB inactivation.
PMID: 8649818 [PubMed - indexed for MEDLINE]
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Cited by 73 PubMed Central articles
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Mammalian MCM loading in late-G(1) coincides with Rb hyperphosphorylation and the transition to post-transcriptional control of progression into S-phase.
Mukherjee P, Cao TV, Winter SL, Alexandrow MG.
PLoS One. 2009; 4(5):e5462. Epub 2009 May 7.
[PLoS One. 2009]
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Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer.
Barbash O, Zamfirova P, Lin DI, Chen X, Yang K, Nakagawa H, Lu F, Rustgi AK, Diehl JA.
Cancer Cell. 2008 Jul 8; 14(1):68-78.
[Cancer Cell. 2008]
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Cyclin E phosphorylation regulates cell proliferation in hematopoietic and epithelial lineages in vivo.
Minella AC, Loeb KR, Knecht A, Welcker M, Varnum-Finney BJ, Bernstein ID, Roberts JM, Clurman BE.
Genes Dev. 2008 Jun 15; 22(12):1677-89.
[Genes Dev. 2008]
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