Mimosine arrests cells in G1 by enhancing the levels of p27(Kip1)

Citation
G. Wang et al., Mimosine arrests cells in G1 by enhancing the levels of p27(Kip1), EXP CELL RE, 254(1), 2000, pp. 64-71
Citations number
37
Categorie Soggetti
Cell & Developmental Biology
Journal title
EXPERIMENTAL CELL RESEARCH
ISSN journal
00144827 → ACNP
Volume
254
Issue
1
Year of publication
2000
Pages
64 - 71
Database
ISI
SICI code
0014-4827(20000110)254:1<64:MACIGB>2.0.ZU;2-G
Abstract
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.