alpha B-crystallin, a small heat shock protein, modulates NF-kappa B activity in a phosphorylation-dependent manner and protects muscle myoblasts from TNF-alpha induced cytotoxicity

作者：Adhikari Amit S; Singh Bhairab N; Rao K Sridhar; Rao Ch Mohan^*

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2011, 1813(8): 1532-1542.

DOI：10.1016/j.bbamcr.2011.04.009

• HSP
• alpha B-crystallin
• TNF-alpha
• NF-kappa B
• Apoptosis
• Differentiation

alpha B-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 alpha B-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 alpha B-crystallin in TNF-alpha induced regulation of NF-kappa B.
We demonstrate that in response to TNF-alpha treatment, alpha B-crystallin associates with IKK beta and activate its kinase activity, facilitating the degradation of phosphorylated I-kB alpha, a prime step in NF-kappa B activation. Reducing the level of alpha B-crystallin using the RNAi approach reduces the translocation of p65, further confirming the role of alpha B-crystallin in NF-kappa B activation. Our study shows that the ability of alpha B-crystallin to activate NF-kappa B depends on its phosphorylation status. The present study shows that alpha B-crystallin-dependent NF-kappa B activation protects myoblasts from TNF-alpha induced cytoxicity by enhancing the expression of the antiapoptotic protein. Bcl 2. Thus, our study identifies yet another mechanism by which alpha B-crystallin exerts its anti-apoptotic activity.

• 出版日期2011-8