A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions.

Developmental Cell
Marta M LipinskiJunying Yuan

Abstract

Autophagy is a cellular catabolic mechanism that plays an essential function in protecting multicellular eukaryotes from neurodegeneration, cancer, and other diseases. However, we still know very little about mechanisms regulating autophagy under normal homeostatic conditions when nutrients are not limiting. In a genome-wide human siRNA screen, we demonstrate that under normal nutrient conditions upregulation of autophagy requires the type III PI3 kinase, but not inhibition of mTORC1, the essential negative regulator of starvation-induced autophagy. We show that a group of growth factors and cytokines inhibit the type III PI3 kinase through multiple pathways, including the MAPK-ERK1/2, Stat3, Akt/Foxo3, and CXCR4/GPCR, which are all known to positively regulate cell growth and proliferation. Our study suggests that the type III PI3 kinase integrates diverse signals to regulate cellular levels of autophagy, and that autophagy and cell proliferation may represent two alternative cell fates that are regulated in a mutually exclusive manner.

References

Jun 6, 2000·Journal of Biomolecular Screening·J H ZhangK R Oldenburg
Apr 3, 2001·Proceedings of the National Academy of Sciences of the United States of America·T ItoY Sakaki
Mar 3, 2004·Nature Reviews. Cancer·P Andrew FutrealMichael R Stratton
Jul 29, 2005·The Journal of Biological Chemistry·Maya P ByfieldJonathan M Backer
Sep 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Takahiro NobukuniGeorge Thomas
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Dec 31, 2005·Nucleic Acids Research·Gopa R MishraAkhilesh Pandey
Mar 9, 2006·The Journal of Biological Chemistry·Mamoru ShibataJunying Yuan
Aug 12, 2006·The Journal of Biological Chemistry·Tomohiro YorimitsuDaniel J Klionsky
Oct 13, 2006·Molecular and Cellular Biology·Maiko OgataKazunori Imaizumi
Dec 1, 2006·Nucleic Acids Research·Andrew Chatr-aryamontriGianni Cesareni
May 19, 2007·Genes & Development·Robin MathewEileen White
Aug 1, 2007·Immunity·Dorothee Schmid, Christian Münz
Sep 25, 2007·Nature Cell Biology·Yoshinori TakahashiHong-Gang Wang
Nov 2, 2007·Nature Reviews. Cancer·Robin MathewEileen White
Nov 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Lihong ZhangJunying Yuan
Jan 15, 2008·Cell·Beth Levine, Guido Kroemer
Jan 25, 2008·Journal of Biomolecular Screening·Namjin ChungBerta Strulovici
May 14, 2008·The Journal of Cell Biology·Gábor JuhászThomas P Neufeld
Jan 20, 2009·The Journal of Biological Chemistry·Carson C ThoreenNathanael S Gray

❮ Previous
Next ❯

Citations

Jul 10, 2012·Molecules and Cells·Soon-Hee KimTaijoon Chung
Jun 25, 2013·Cancer Letters·Zheng ShiJin-ku Bao
Jun 4, 2013·Seminars in Cancer Biology·Martina WirthSharon A Tooze
Jun 4, 2013·Seminars in Cancer Biology·Federico PietrocolaGuido Kroemer
Dec 23, 2011·Cell Death & Disease·M ChiongS Lavandero
Jan 21, 2011·Nature·Beth LevineHerbert W Virgin
Sep 3, 2010·Nature Cell Biology·Zhifen Yang, Daniel J Klionsky
Mar 2, 2011·Nature Reviews. Drug Discovery·Oliver KeppGuido Kroemer
Dec 12, 2013·Nature Reviews. Molecular Cell Biology·Jens FüllgrabeBertrand Joseph
Jul 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Marta M LipinskiJunying Yuan
Apr 30, 2011·Briefings in Functional Genomics·Ming JiangMichael Howell
Oct 16, 2010·Journal of Molecular Cell Biology·Steven K Backues, Daniel J Klionsky
Jun 5, 2012·Cold Spring Harbor Perspectives in Biology·Gautam DasEric H Baehrecke
Oct 15, 2011·Pigment Cell & Melanoma Research·Agnieszka Checinska, María S Soengas
Jun 2, 2011·Molecular and Cellular Biology·Peter J Roach
Apr 18, 2013·Biochemistry. Biokhimii︠a︡·A A ParkhitkoE P Henske
May 15, 2013·Annual Review of Genomics and Human Genetics·Maria Antonietta De MatteisCathal Wilson
May 23, 2012·AIDS Research and Therapy·M Scott Killian
Jun 1, 2012·Journal of Cell Science·Thomas P Neufeld
Jan 30, 2014·PloS One·Laura PoilletGilles Despouy
May 15, 2012·Haematologica·Lauren I Aronson, Faith E Davies
Oct 14, 2011·Viruses·Vanessa M Hubbard, Ken Cadwell
Mar 28, 2012·Annual Review of Immunology·Petric KuballaRamnik J Xavier
Sep 3, 2014·Assay and Drug Development Technologies·Nur Akmarina B M SaidElizabeth D Williams
Dec 12, 2012·Annual Review of Physiology·Khushbu K Patel, Thaddeus S Stappenbeck
Nov 25, 2014·Nature Cell Biology·Bin GuoHong Zhang
Oct 20, 2014·Nature Chemical Biology·Baptiste RonanBenoit Pasquier
Sep 16, 2010·Seminars in Immunopathology·Aylwin C Y Ng
Aug 7, 2012·Expert Opinion on Therapeutic Patents·Pierre BischoffFrancis J Dumont
Jan 19, 2016·Biochimica Et Biophysica Acta·Carl WardViktor I Korolchuk
Dec 15, 2015·Cellular and Molecular Life Sciences : CMLS·Benoit Pasquier
Jan 19, 2016·Biochimica Et Biophysica Acta·Ge LiYingyu Chen
Jun 21, 2014·BioMed Research International·Nitha C MulakkalIoannis P Nezis
Feb 7, 2012·New Biotechnology·Kaylene J SimpsonPeter R Boag
Oct 29, 2015·Autophagy·Patricia PrietoLisardo Boscá

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy Networks

Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.

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

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.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Bacterial Transport Proteins

Bacterial transport proteins facilitate active and passive transport of small molecules and solutes across the bacterial membrane. Here is the latest research.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.