Cyclin D3 is rate-limiting for the G1/S phase transition in fibroblasts.
D-type cyclins are induced in response to mitogens and are believed to control progression through the G1 phase of the cell cycle by activating their corresponding kinase partners (cyclin-dependent kinases). To investigate the function of individual D-type cyclins we have constructed rat fibroblast lines that allow controllable overexpression of a human cyclin D3 cDNA. Overexpression of cyclin D3 led to accelerated passage through G1 in actively proliferating cells with no effect on the overall population doubling time. In cells re-entering the division cycle from a quiescent state, cyclin D3 caused an even more dramatic advancement of S phase entry. Accelerated progression through G0/G1-to-S correlated with premature phosphorylation of the pRb tumor suppressor protein and its relatives, p107 and p130. We conclude that cyclin D3 can act as a rate-limiting G1 cyclin and that this effect involves, in part, the premature phosphorylation of critical substrates.
Herzinger
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Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Reed
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SI
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D056743:Cyclin D3; D016213:Cyclins / Q000502:physiology*; D016193:G1 Phase / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D010766:Phosphorylation; D051381:Rats; D016160:Retinoblastoma Protein / Q000032:analysis; D016196:S Phase / Q000502:physiology; D013752:Tetracycline / Q000494:pharmacology
C534696:CCND3 protein, human; C534698:Ccnd3 protein, rat; D056743:Cyclin D3; D016213:Cyclins; D016160:Retinoblastoma Protein; D013752:Tetracycline