Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10748939 | Biochemical and Biophysical Research Communications | 2016 | 7 Pages |
Abstract
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.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Liujing Qu, Ge Li, Dan Xia, Beiqi Hongdu, Chentong Xu, Xin Lin, Yingyu Chen,