US EPA

1579240 

Journal Article 

p27 Suppresses cyclooxygenase-2 expression by inhibiting p38β and p38δ-mediated CREB phosphorylation upon arsenite exposure 

Che, X; Liu, J; Huang, H; Mi, X; Xia, Q; Li, J; Zhang, D; Ke, Q; Gao, J; Huang, C 

2013 

1 

Biochimica et Biophysica Acta
ISSN: 0006-3002
EISSN: 1878-2434 

1833 

9 

2083-2091 

English 

23639288 

10.1016/j.bbamcr.2013.04.012 

WOS:000321173900006 

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. 

p27; COX-2; p38; CREB; Arsenite