| First Author | Che X | Year | 2013 |
| Journal | Biochim Biophys Acta | Volume | 1833 |
| Issue | 9 | Pages | 2083-91 |
| PubMed ID | 23639288 | Mgi Jnum | J:202386 |
| Mgi Id | MGI:5518971 | Doi | 10.1016/j.bbamcr.2013.04.012 |
| Citation | Che X, et al. (2013) p27 suppresses cyclooxygenase-2 expression by inhibiting p38beta and p38delta-mediated CREB phosphorylation upon arsenite exposure. Biochim Biophys Acta 1833(9):2083-91 |
| abstractText | 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 p38beta and p38delta. 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. |
