Involvement of p27(kip1) and cyclin D3 in the regulation of cdk2 activity during skeletal muscle differentiation.
Terminal myogenic differentiation involves an irreversible transition from a proliferative state to a post-mitotic quiescent state. We showed here that in addition to the previously reported down regulation of G(1)-related cyclin-associated kinase activities, this transition was also accompanied by an extensive reorganization of the cyclin-cdk complexes, including a dramatic shift of cdk2 from cyclin A to cyclin D3. Moreover, the inhibition of cdk activity also correlated with an increase in the expression of the p27(kip1) cdk inhibitor and in its association with the cyclin-cdk2 complexes. Since depletion of p27 substantially reduced the cdk inhibitor activity present in differentiated muscle cells, we believe that the increase in p27 expression along with the reorganization of the cyclin-cdk2 complexes may play an important role in the inhibition of cdk2 activity during the differentiation process.
Chu
C Y
CY
Department of Pharmacology, University of Missouri-Columbia, MO 65212, Columbia, USA.
Lim
R W
RW
D000818:Animals; D000906:Antibodies / Q000276:immunology; D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002460:Cell Line; D056743:Cyclin D3; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016213:Cyclins / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D000906:Antibodies; C534697:Ccnd3 protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D056743:Cyclin D3; D016213:Cyclins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases