Loss of cell adhesion lo substratum up-regulates p21(Cip1/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, p27(Kip1), was down-regulated by growth factors in serum, and this down-regulation was partially prevented by loss of cell adhesion, Another CDK2 inhibitor, p21(Cip1/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 p21(Cip1/WAF1) expression but did not affect the abundance of p27(Kip1), These results suggest that loss of cell adhesion to substratum up-regulates p21(Cip1/WAF1) expression, which plays an essential role for arresting the BALB/c 3T3 fibroblast cell cycle, (C) 1997 Academic Press.