title: PRKCI negatively regulates autophagy via PIK3CA/AKT-MTOR signaling.
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.
authors.affiliation: 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.
authors.forename: Liujing
authors.initials: L
authors.lastname: Qu
authors.affiliation: 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.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Dan
authors.initials: D
authors.lastname: Xia
authors.affiliation: 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.
authors.forename: Beiqi
authors.initials: B
authors.lastname: Hongdu
authors.affiliation: 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.
authors.forename: Chentong
authors.initials: C
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D001343:Autophagy; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000099293:Protein Kinase C-lambda
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D000099293:Protein Kinase C-lambda; C546842:MTOR protein, human; C484760:PIK3CA protein, human
keywords: Autophagy; MTOR; PRKCI