The plant amino acid mimosine, an effective inhibitor of DNA replication, h
as been demonstrated to arrest cell cycle progression in late G1, To unders
tand further the molecular mechanism by which mimosine affects the cell cyc
le, we treated quiescent cells with serum in the presence of 800 mu M mimos
ine, The cells did not enter S phase and were completely arrested in G1 pha
se. Although neither the mitogenic induction of the G1 cyclins nor the prot
ein levels of cdk2 or cdk4 were affected, serum-dependent activation of cdk
2 was blocked. This corresponded to elevated levels of the cdk inhibitor p2
7(Kip1). This was not mediated through inhibition of degradation but rather
involved increased synthesis of both p27(Kip1) mRNA and protein. Mimosine
did not appear to affect mitogen-dependent signals that normally lead to p2
7(Kip1) downregulation since the inhibitor was induced to even greater leve
ls in quiescent, unstimulated cells. In the presence of mimosine, actinomyc
in D treatment for 2 h prevented the increase of p27(Kip1) mRNA, but p27(Ki
p1) protein levels were still enhanced under these conditions. We propose t
hat mimosine blocks the cell cycle in late G1 phase by upregulation of p27(
Kip1) protein levels through transcriptional and posttranscriptional regula
tory mechanisms, (C) (2000) Academic Press.