PRKCI negatively regulates autophagy via PIK3CA/AKT–MTOR signaling

The atypical protein kinase C isoform PRKC iota (PRKCI) plays a key role in cell proliferation, differentiation, and carcinogenesis, and it has been shown to be a human oncogene. Here, we show that PRKCI overexpression in U2OS cells impaired functional autophagy in normal or cell stress conditions, as characterized by decreased levels of light chain 3B-II protein (LC3B-II) and weakened degradation of endogenous and exogenous autophagic substrates. Conversely, PRKCI knockdown by small interference RNA resulted in opposite effects. Additionally, we identified two novel PRKCI mutants, PRKCIL485M and PRKCIP560R, which induced autophagy and exhibited dominant negative effects. Further studies indicated that PRKCI knockdown–mediated autophagy was associated with the inactivation of phosphatidylinositol 3-kinase alpha/AKT–mammalian target of rapamycin (PIK3CA/AKT–MTOR) signaling. These data underscore the importance of PRKCI in the regulation of autophagy. Moreover, the finding may be useful in treating PRKCI-overexpressing carcinomas that are characterized by increased levels of autophagy. •The atypical protein kinase C iota isoform (PRKCI) is a human oncogene.•PRKCI overexpression impairs functional autophagy in U2OS cells.•It reduces LC3B-II levels and weakens SQSTM1 and polyQ80 aggregate degradation.•PRKCI knockdown has the opposite effect.•The effect of PRKCI knockdown is related to PIK3CA/AKT–MTOR signaling inactivation.