PRKCI negatively regulates autophagy via PIK3CA/AKT-MTOR signaling

Liujing Qu; Ge Li; Dan Xia; Beiqi Hongdu; Chentong Xu; Xin Lin; Yingyu Chen

doi:10.1016/j.bbrc.2016.01.059

PRKCI negatively regulates autophagy via PIK3CA/AKT-MTOR signaling

Biochem Biophys Res Commun. 2016 Feb 5;470(2):306-312. doi: 10.1016/j.bbrc.2016.01.059. Epub 2016 Jan 11.

Authors

Liujing Qu¹, Ge Li¹, Dan Xia¹, Beiqi Hongdu¹, Chentong Xu¹, Xin Lin¹, Yingyu Chen²

Affiliations

¹ Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Sciences Center, Beijing, China; Peking University Center for Human Disease Genomics, Peking University, Beijing, China.
² Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Sciences Center, Beijing, China; Peking University Center for Human Disease Genomics, Peking University, Beijing, China. Electronic address: yingyu_chen@bjmu.edu.cn.

PMID: 26792725
DOI: 10.1016/j.bbrc.2016.01.059

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, PRKCI(L485M) and PRKCI(P560R), 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.

Keywords: Autophagy; MTOR; PRKCI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy*
Cell Line, Tumor
Class I Phosphatidylinositol 3-Kinases
Humans
Isoenzymes / metabolism*
Osteosarcoma / metabolism*
Osteosarcoma / pathology
Phosphatidylinositol 3-Kinases / metabolism*
Protein Kinase C / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction
TOR Serine-Threonine Kinases / metabolism*

Substances

Isoenzymes
MTOR protein, human
Class I Phosphatidylinositol 3-Kinases
PIK3CA protein, human
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
Protein Kinase C
protein kinase C lambda