INDUCTION OF CYCLIN-E AND CYCLIN-A IN RESPONSE TO MITOGEN REMOVAL - ABASIC ALTERATION ASSOCIATED WITH THE ARREST OF DIFFERENTIATION OF C2 MYOBLASTS TRANSFORMED BY SIMIAN-VIRUS-40 LARGE T-ANTIGEN
D. Tedesco et al., INDUCTION OF CYCLIN-E AND CYCLIN-A IN RESPONSE TO MITOGEN REMOVAL - ABASIC ALTERATION ASSOCIATED WITH THE ARREST OF DIFFERENTIATION OF C2 MYOBLASTS TRANSFORMED BY SIMIAN-VIRUS-40 LARGE T-ANTIGEN, Journal of virology, 71(3), 1997, pp. 2217-2224
We previously showed that C2 myoblasts transformed by simian virus 40
large T antigen (SVLT) stop the myogenic process after the induction o
f myogenin and of high Rb levels; the induced Rb, however, becomes not
ably phosphorylated. We have analyzed the protein levels and activitie
s of cyclin-dependent kinases (cdks) in untransformed C2 cells and in
transformants of either SVLT or the cytoplasmic mutant NKT1 (which per
mits differentiation) upon a shift from growth medium (GM) to mitogen-
poor differentiation medium (DM). After the shift, cdk4 levels remaine
d constant and cdk6 levels decreased in all cell types; cdk2 minimally
increased only in SVLT cells. Cyclin D1 was downregulated in DM in al
l cell types, and cyclin D3 was upregulated (albeit less strongly in S
VLT cells than in the others). In contrast, a dramatic difference betw
een SVLT cells and the other cells was observed for cyclins E and A, w
hich essentially disappeared (as protein and RNA) in normal C2 and NKT
1 cells upon the shift from GM to DM, whereas they increased in SVLT c
ells. Concurrently, cdk2 activity ceased in C2 and NKT1 cells in DM, w
hereas it persisted at 20% of the GM level in SVLT cells. cdk4 activit
y was detectable in all cells only in GM. Cyclin E and A induction thu
s appeared to sustain enough Rb phosphorylation to interfere with tiss
ue-specific expression, with cdk activity not high enough to activate
cyclin self-regulation. In DM, cdk2 complexed to D3 was underphosphory
lated in all cells, and SVLT allowed strong inductions of p21 and p27
without affecting their complexes with cdks.