Loss of cell adhesion to substratum up-regulates p21Cip1/WAF1 expression in BALB/c 3T3 fibroblasts.
Cell adhesion to substratum is essential for the transition of G1 to S phase in mouse BALB/c 3T3 fibroblast cell cycle. Loss of cell adhesion in late G1 phase caused blockage of the G1/S phase transition and repression of cyclin E-associated cyclin-dependent kinase-2 (CDK2) activity. A CDK2 inhibitor abundant in quiescent cells, p27Kip1, was down-regulated by growth factors in serum, and this down-regulation was partially prevented by loss of cell adhesion. Another CDK2 inhibitor, p21Cip1/WAF1, which was undetectable in quiescent cells, was markedly induced by loss of cell adhesion. In exponentially growing cells, loss of cell adhesion also induced p21Cip1/WAF1 expression but did not affect the abundance of p27Kip1. These results suggest that loss of cell adhesion to substratum up-regulates p21Cip1/WAF1 expression, which plays an essential role for arresting the BALB/c 3T3 fibroblast cell cycle.
Kuzumaki
T
T
Department of Biochemistry, Yamagata University School of Medicine, Japan. kuzumaki@med.id.yamagata-u.ac.jp
Ishikawa
K
K
D016475:3T3 Cells; D000818:Animals; D042846:CDC2-CDC28 Kinases; D002448:Cell Adhesion; D018797:Cell Cycle Proteins; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016213:Cyclins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D016193:G1 Phase; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016196:S Phase; D013379:Substrate Specificity; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation / Q000502:physiology*
C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; 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