p62 modulates the intrinsic signaling of UVB-induced apoptosis

• P62-deficient cells are more resistant to UVB-induced apoptosis than normal cells.
• Bcl-2 family expression and Stat3 phosphorylation are changed in p62-deficient cells.
• P62 modulates the intrinsic signaling pathway of UVB-induced apoptosis.

BackgroundUVB radiation is the main source of sunburn and skin cancers. Apoptosis eliminates photodamaged cells, and is thus important for preventing epidermal carcinogenesis. The cytoplasmic regulatory protein p62/A170/sequestosome 1 (p62) molecule is involved in a variety of cellular and signaling pathways. p62 is known to be and important in autophagy, but its role in UVB-induced apoptosis remains to be clarified.ObjectiveTo investigate the role of p62 against UVB-induced apoptotic changes, using mouse embryonic fibroblasts (MEFs) derived from p62 homozygous knockout (p62−/−) mice.Methodsp62−/− and wild-type (p62+/+) mice and MEFs were subjected to UVB irradiation, and the resultant apoptosis was analyzed using flow cytometry, quantitative real-time PCR, and western blots.ResultsApoptosis was decreased in the p62−/− MEFs compared to p62+/+ MEFs in response to UVB treatment. Compared with p62+/+ MEFs, p62−/− MEFs expressed significantly more Bcl-2 and less Bax, and showed increased Src and Stat3 phosphorylation. Our results show that p62 regulates apoptotic pathways by modifying critical signaling intermediates such as Src and Stat3.Conclusionp62 reduces UVB-induced apoptosis by modulating intrinsic apoptotic signaling through Src phosphorylation.