Molecular stop signs: regulation of cell-cycle arrest by C/EBP transcription factors.
The CCAAT/enhancer-binding protein (C/EBP) family of transcription factors plays an important role in controlling cell proliferation and differentiation. C/EBPalpha is a particularly potent regulator of cell-cycle exit and is induced in terminally differentiating adipocytes and myeloid cells, where it also activates differentiation-specific genes. The growth-inhibiting activity of C/EBPalpha suppresses tumorigenesis in myeloid cells and possibly other tissues. In addition, recent work has identified C/EBPalpha as a component of the p53-regulated growth arrest response elicited by DNA damage in epidermal keratinocytes. Several studies have explored the mechanism by which C/EBPalpha blocks cell-cycle progression at the G1-S boundary, and several models have been proposed but no universally accepted mechanism has emerged. Controversial issues include whether C/EBPalpha acts through an 'off-DNA' mechanism to inhibit cyclin-dependent kinases, and whether and how it functions with the RB-E2F system to repress transcription of S-phase genes. Other C/EBP-family members have also been implicated in positive and negative control of cell proliferation, and the mechanisms underlying their growth-regulatory activities are beginning to be elucidated.
Johnson
Peter F
PF
Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, NCI-Frederick, MD 21702-1201, USA. johnsopf@ncifcrf.gov
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology
D022762:CCAAT-Enhancer-Binding Proteins