Phosphorylation of heat shock protein 27 antagonizes TNF-α induced HeLa cell apoptosis via regulating TAK1 ubiquitination and activation of p38 and ERK signaling.

摘要: Tumor necrosis factor (TNF)-α is a potent cytokine that regulates critical cellular processes including apoptosis. TNF-α usually triggers both survival and apoptotic signals in various cell types. Heat shock protein 27 (HSP27), an important chaperone, believed to protect cells from HSP27 can be phosphorylated changed its function according different stimuli. However, available reports on the role of phosphorylation apoptosis remain elusive. In this study, we investigated induced human cervical carcinoma (HeLa) cells. We found was enhanced if suppressed by specific inhibitor CMPD1 or MAPKAPK2 (MK2) knockdown overexpression non-phosphorylatable mutant HSP27-3A. Through co-immunoprecipitation confocal microscopy, observed associated with transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) response stimulation. By blocking MK2 activity overexpressing phospho-mimetic Hsp27-3D, further showed facilitated ubiquitination TAK1 activations p38 MAPK ERK, downstream pro-survival signaling. addition, also increased inhibited TRADD but did not influence binding between FADD pro-apoptotic complex. Taken together, our data indicated involved modulating via interacting regulating post-translational modifications HeLa This study demonstrates serves as novel regulator TNF-α-induced apoptosis, provides new insight into cytoprotective phosphorylation.