| First Author | Adhikari AS | Year | 2011 |
| Journal | Biochim Biophys Acta | Volume | 1813 |
| Issue | 8 | Pages | 1532-42 |
| PubMed ID | 21640763 | Mgi Jnum | J:177749 |
| Mgi Id | MGI:5295925 | Doi | 10.1016/j.bbamcr.2011.04.009 |
| Citation | Adhikari AS, et al. (2011) alphaB-crystallin, a small heat shock protein, modulates NF-kappaB activity in a phosphorylation-dependent manner and protects muscle myoblasts from TNF-alpha induced cytotoxicity. Biochim Biophys Acta 1813(8):1532-42 |
| abstractText | alphaB-crystallin, a member of the small heat shock protein family, has been implicated in various biological functions including response to heat shock, differentiation and apoptosis, the mechanisms of which have not been well understood. Myoblasts, the precursor cells in muscle regeneration, when subjected to growth factor deprivation differentiate to form myotubes or undergo apoptosis. During differentiation, myoblasts express elevated levels of alphaB-crystallin as well as TNF-alpha but the connecting link between these proteins in cell signaling is not clearly understood. We have therefore investigated the role of alphaB-crystallin in TNF-alpha induced regulation of NF-kappaB. We demonstrate that in response to TNF-alpha treatment, alphaB-crystallin associates with IKKbeta and activate its kinase activity, facilitating the degradation of phosphorylated I-kBalpha, a prime step in NF-kappaB activation. Reducing the level of alphaB-crystallin using the RNAi approach reduces the translocation of p65, further confirming the role of alphaB-crystallin in NF-kappaB activation. Our study shows that the ability of alphaB-crystallin to activate NF-kappaB depends on its phosphorylation status. The present study shows that alphaB-crystallin-dependent NF-kappaB activation protects myoblasts from TNF-alpha induced cytoxicity by enhancing the expression of the anti-apoptotic protein, Bcl 2. Thus, our study identifies yet another mechanism by which alphaB-crystallin exerts its anti-apoptotic activity. |
