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• W2113058656 endingPage "2582" @default.
• W2113058656 startingPage "2570" @default.
• W2113058656 abstract "ABSTRACT C/EBPα arrests proliferation of young livers by inhibition of cdk2. In old mice, C/EBPα inhibits growth by repression of E2F-dependent promoters through the C/EBPα-Brm complex. In this paper, we show that cyclin D3-cdk4/cdk6 supports the ability of C/EBPα to inhibit liver proliferation in both age groups. Although cyclin D3-cdk4/cdk6 kinases are involved in the promotion of growth, they are expressed in terminally differentiated cells, suggesting that they have additional functions in these settings. We demonstrate that C/EBPα represents a target for phosphorylation by cyclin D3-cdk4/cdk6 complexes in differentiated liver cells and in differentiated adipocytes. Cyclin D3-cdk4/cdk6 specifically phosphorylate C/EBPα at Ser193 in vitro and in the liver and support growth-inhibitory C/EBPα-cdk2 and C/EBPα-Brm complexes. We found that cyclin D3 is increased in old livers and activates cdk4/cdk6, resulting in stabilization of the C/EBPα-Brm complex. Old livers fail to reduce the activity of cyclin D3-cdk4/cdk6 after partial hepatectomy, leading to high levels of C/EBPα-Brm complexes after partial hepatectomy, which correlate with weak proliferation. We examined the role of cyclin D3 in the stabilization of C/EBPα-cdk2 and C/EBPα-Brm by using 3T3-L1 differentiated cells. In these cells, cyclin D3 is increased during differentiation and phosphorylates C/EBPα at Ser193, leading to the formation of growth-inhibitory C/EBPα-cdk2 and C/EBPα-Brm complexes. The inhibition of cyclin D3 blocks the formation of these complexes. Thus, these studies provide a new function of cyclin D3, which is to support the growth-inhibitory activity of C/EBPα." @default.
• W2113058656 created "2016-06-24" @default.
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• W2113058656 date "2006-04-01" @default.
• W2113058656 modified "2023-09-25" @default.
• W2113058656 title "Cyclin D3 Maintains Growth-Inhibitory Activity of C/EBPα by Stabilizing C/EBPα-cdk2 and C/EBPα-Brm Complexes" @default.
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• W2113058656 doi "https://doi.org/10.1128/mcb.26.7.2570-2582.2006" @default.
• W2113058656 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1430318" @default.
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