Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10802294 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2013 | 39 Pages |
Abstract
p27 is a cyclin-dependent kinase (CDK) inhibitor that suppresses a cell's transition from G0 to S phase, therefore acting as a tumor suppressor. Our most recent studies demonstrate that upon arsenite exposure, p27 suppresses Hsp27 and Hsp70 expressions through the JNK2/c-Jun- and HSF-1-dependent pathways, suggesting a novel molecular mechanism underlying the tumor suppressive function of p27 in a CDK-independent manner. We found that p27-deficiency (p27 â/â) resulted in the elevation of cyclooxygenase-2 (COX-2) expression at transcriptional level, whereas the introduction of p27 brought back COX-2 expression to a level similar to that of p27 +/+ cells, suggesting that p27 exhibits an inhibitory effect on COX-2 expression. Further studies identified that p27 inhibition of COX-2 expression was specifically due to phosphorylation of transcription factor cAMP response element binding (CREB) phosphorylation mediated by p38β and p38δ. These results demonstrate a novel mechanism underlying tumor suppression effect of p27 and will contribute to the understanding of the overall mechanism of p27 tumor suppression in a CDK-independent manner.
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Authors
Xun Che, Jinyi Liu, Haishan Huang, Xiaoyi Mi, Qing Xia, Jingxia Li, Dongyun Zhang, Qingdong Ke, Jimin Gao, Chuanshu Huang,