p27 suppresses cyclooxygenase-2 expression by inhibiting p38β and p38δ-mediated CREB phosphorylation upon arsenite exposure.
p27 suppresses cyclooxygenase-2 expression by inhibiting p38β and p38δ-mediated CREB phosphorylation upon arsenite exposure.
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DOI：
10.1016/j.bbamcr.2013.04.012
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发表时间：
2013-09
影响因子：
5.1
通讯作者：
Huang, Chuanshu
中科院分区：
文献类型：
--
作者：
Che, Xun;Liu, Jinyi;Huang, Haishan;Mi, Xiaoyi;Xia, Qing;Li, Jingxia;Zhang, Dongyun;Ke, Qingdong;Gao, Jimin;Huang, Chuanshu
P27是一种细胞周期蛋白依赖性激酶抑制物，可以抑制细胞从G0期向S期的转变，从而起到肿瘤抑制的作用。我们最近的研究表明，在亚砷酸盐暴露后，p27通过依赖JNK2/c-jun和HSF-1的途径抑制Hsp27和Hsp70的表达，这表明p27以CDK不依赖的方式抑制肿瘤功能。我们发现，p27缺失(p27−/−)导致环氧合酶-2(COX-2)在转录水平的表达增加，而p27的引入使COX-2的表达恢复到与p27+/+细胞相似的水平，表明p27对COX-2的表达具有抑制作用。进一步的研究证实，p27抑制COX-2的表达是由于p38β和p38δ介导的转录因子cAMP反应元件结合蛋白的磷酸化。这些结果证明了p27抑瘤作用的新机制，并将有助于理解p27以CDK非依赖性方式抑制肿瘤的整体机制。
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−/−) 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 understanding of the overall mechanism of p27 tumor suppression in a CDK-independent manner.
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影响因子：
56.9
作者：
HAN, J;LEE, JD;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
影响因子：
4.3
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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