title: αB-crystallin, a small heat shock protein, modulates NF-κB activity in a phosphorylation-dependent manner and protects muscle myoblasts from TNF-α induced cytotoxicity.
abstract: αB-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 αB-crystallin as well as TNF-α but the connecting link between these proteins in cell signaling is not clearly understood. We have therefore investigated the role of αB-crystallin in TNF-α induced regulation of NF-κB. We demonstrate that in response to TNF-α treatment, αB-crystallin associates with IKKβ and activate its kinase activity, facilitating the degradation of phosphorylated I-kBα, a prime step in NF-κB activation. Reducing the level of αB-crystallin using the RNAi approach reduces the translocation of p65, further confirming the role of αB-crystallin in NF-κB activation. Our study shows that the ability of αB-crystallin to activate NF-κB depends on its phosphorylation status. The present study shows that αB-crystallin-dependent NF-κB activation protects myoblasts from TNF-α induced cytoxicity by enhancing the expression of the anti-apoptotic protein, Bcl 2. Thus, our study identifies yet another mechanism by which αB-crystallin exerts its anti-apoptotic activity.
authors.affiliation: Centre for cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad 500 007, India.
authors.forename: Amit S
authors.initials: AS
authors.lastname: Adhikari
authors.forename: Bhairab N
authors.initials: BN
authors.lastname: Singh
authors.forename: K Sridhar
authors.initials: KS
authors.lastname: Rao
authors.forename: Ch Mohan
authors.initials: ChM
authors.lastname: Rao
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D050888:Heat-Shock Proteins, Small / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D012694:Serine / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity; D038203:alpha-Crystallin B Chain / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D050888:Heat-Shock Proteins, Small; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D014409:Tumor Necrosis Factor-alpha; D038203:alpha-Crystallin B Chain; D000072000:NF-KappaB Inhibitor alpha; D012694:Serine; D051550:I-kappa B Kinase