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Fig. 3. Models of C/EBP{alpha}-induced cell-cycle arrest. The figure shows key events regulating G1-S progression during the mitotic cycle. Activation of CDK4/CDK6 and, later, CDK2 by induction of cyclins leads to phosphorylation of pRB and its release from E2F transcription factors. CDK inhibitors such as p21 can block this step. Dissociation of phosphorylated pRB relieves repression of S-phase genes, which are otherwise inhibited by pRB-E2F through recruitment of the SWI/SNF chromatin-remodeling complex and histone deacetylases (not shown). The models of C/EBP{alpha} action fall into two categories: direct or p21-dependent inhibition of CDK activity (non-transcriptional) and repression of S-phase genes (transcriptional). C/EBP{alpha} may be tethered to target S-phase gene promoters indirectly by E2F or it could bind directly to E2F sites. Alternatively, S-phase genes might contain C/EBP-binding sites in their promoters (not shown).





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