PRKCI negatively regulates autophagy via PIK3CA/AKT-MTOR signaling

Biochemical and Biophysical Research Communications
Liujing QuYingyu Chen

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.

References

Mar 27, 2007·Nature Reviews. Cancer·Erin M Griner, Marcelo G Kazanietz
Nov 2, 2007·Nature Reviews. Cancer·Robin MathewEileen White
Sep 10, 2008·Cancer Treatment Reviews·Ashhar S AliFazlul H Sarkar
Jun 30, 2009·Molecular Oncology·Andreas BrechHarald Stenmark
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
Sep 12, 2012·Autophagy·Daniel J KlionskyBrian Zuckerbraun
Dec 12, 2012·Cell Stress & Chaperones·Bo-Shi WangMing-Rong Wang
Nov 16, 2013·Biochemical Pharmacology·Peter J ParkerAlan P Fields

❮ Previous
Next ❯

Citations

Aug 18, 2018·Journal of Cancer Research and Clinical Oncology·Tianyi WangLili Jia
May 2, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Wen-Jun WangCheng Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms