| First Author | Guo W | Year | 2014 |
| Journal | Biochem Biophys Res Commun | Volume | 447 |
| Issue | 4 | Pages | 563-8 |
| PubMed ID | 24751519 | Mgi Jnum | J:219454 |
| Mgi Id | MGI:5620851 | Doi | 10.1016/j.bbrc.2014.04.055 |
| Citation | Guo W, et al. (2014) IKK-beta/NF-kappaB p65 mediates p27(Kip1) protein degradation in arsenite response. Biochem Biophys Res Commun 447(4):563-8 |
| abstractText | p27(Kip1) is a potent inhibitor of the cyclin-dependent kinases that drive G1 to S phase transition. Since deregulation of p27(Kip1) is found in many malignancies and is associated with the poor prognosis, elucidation of the molecular bases for regulation of p27(Kip1) expression is of great significance, not only in providing insight into the understanding of biological p27(Kip1), but also in the development of new cancer therapeutic tactics. We here explored the inhibitory regulation of IKKbeta on p27(Kip1) expression following arsenite exposure. We found that although the basal level of p27(Kip1) expression in the IKKbeta(-/-) cells is much lower than that in the IKKbeta(+/+) cells, the deletion of IKKbeta in the MEFs led to a marked increase in p27(Kip1) protein induction due to arsenite exposure in comparison to that in the IKKbeta(+/+) cells. The IKKbeta regulatory effect on p27(Kip1) expression was also verified in the IKKbeta(-/-) and IKKbeta(-/-) cells with IKKbeta reconstitutional expression, IKKbeta(-/-) (IKKbeta). Further studies indicated that IKKbeta-mediated p27(Kip1) downregulation occurred at protein degradation level via p65-dependent and p50-independent manner. Moreover, the results obtained from the comparison of arsenite-induced GSK3beta activation among transfectants of WT, IKKbeta(-/-) and IKKbeta(-/-) (IKKbeta), and the utilization of GSKbeta shRNA, demonstrated that IKKbeta regulation of p27 protein degradation was mediated by GSK3beta following arsenite exposure. |
