| 17373649 |
Li JP, Yang JL: Cyclin B1 proteolysis via p38 MAPK signaling participates in G2 checkpoint elicited by arsenite. J Cell Physiol. 2007 Aug;212(2):481-8.
Timely induction of cyclin B1 controls mitotic entry, whereas its proteolysis is essential for mitotic exit. By contrast, cyclin B1 transcription is repressed during G (2) arrest induced by DNA damage. The p38 mitogen-activated protein kinase is involved in the G (2) checkpoint; yet, its impact on cyclin B1 protein levels remains unclear. Here we show that untimely proteolysis of cyclin B1 following p38 activation contributes to G (2) checkpoint. Exposing early G (2) cells to arsenite impeded cyclin B1 protein accumulation, Cdk1 activation, and G (2)-to-M progression. Conversely, cyclin B1 was non-degradable in late G (2) and mitotic cells after arsenite. Cyclin B1 proteolysis was enhanced by arsenite in early G (2) and asynchronous cells. This rapid destruction of cyclin B1 was mediated via the ubiquitin-proteasome pathway probably in a Cdc20 and Cdh1 independent mechanism. Under arsenite, inhibition of p38 activation or depletion of p38alpha suppressed cyclin B1 ubiquitination and proteolysis, while forced expression of MKK6-p38 accelerated these events. Inactivation of p38 in arsenite-treated early G (2) cells allowed G (2)-to-M progression, blocked apoptosis, increased cell viability, and decreased micronucleus formation. Thus, p38 signaling pathway triggering cyclin B1 proteolysis after arsenite may play an important role in connecting G (2) arrest with apoptosis or genome instability. |
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