Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome

Genes & Development
Michael N CorradettiKun-Liang Guan

Abstract

Tuberous sclerosis complex (TSC) and Peutz-Jeghers syndrome (PJS) are dominantly inherited benign tumor syndromes that share striking histopathological similarities. Here we show that LKB1, the gene mutated in PJS, acts as a tumor suppressor by activating TSC2, the gene mutated in TSC. Like TSC2, LKB1 inhibits the phosphorylation of the key translational regulators S6K and 4EBP1. Furthermore, we show that LKB1 activates TSC2 through the AMP-dependent protein kinase (AMPK), indicating that LKB1 plays a role in cell growth regulation in response to cellular energy levels. Our results suggest that PJS and other benign tumor syndromes could be caused by dysregulation of the TSC2/mTOR pathway.

References

Jan 1, 1988·Gastroenterology·G DevroedeP S Herman
Sep 23, 1998·Molecular Medicine Today·J Young, S Povey
Aug 18, 2001·Science·A YlikorkalaT P Mäkelä
Oct 17, 2001·The Journal of Clinical Investigation·G ZhouD E Moller
Nov 3, 2001·Science·P B DennisG Thomas
Dec 18, 2001·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·D G Hardie, S A Hawley
Aug 13, 2002·Nature Cell Biology·Ken InokiKun-Liang Guan
Aug 13, 2002·Nature Cell Biology·Christopher J PotterTian Xu
Jan 31, 2003·Annals of Human Genetics·D J Kwiatkowski
Feb 4, 2003·Nature Reviews. Molecular Cell Biology·Estela Jacinto, Michael N Hall
Jul 9, 2003·Proceedings of the National Academy of Sciences of the United States of America·Seung-Pyo HongMarian Carlson
Aug 7, 2003·Current Opinion in Pharmacology·Shile Huang, Peter J Houghton
Aug 26, 2003·Human Mutation·Charis Eng
Sep 6, 2003·Cancer Cell·James B BrugarolasWilliam G Kaelin
Oct 11, 2003·Molecular Cell·Alykhan F ShamjiStuart L Schreiber
Nov 15, 2003·Current Biology : CB·Angela WoodsDavid Carling
Feb 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Reuben J ShawLewis C Cantley

❮ Previous
Next ❯

Citations

Jul 12, 2012·Cellular and Molecular Life Sciences : CMLS·Junmin PanErica A Golemis
Apr 22, 2009·International Journal of Colorectal Disease·Hui-Min Chen, Jing-Yuan Fang
May 31, 2006·Acta Neuropathologica·Nicoletta RestaGinevra Guanti
Feb 26, 2005·Molecular Genetics and Genomics : MGG·Nathalie Lin-MarqStylianos E Antonarakis
Jan 28, 2009·Apoptosis : an International Journal on Programmed Cell Death·Avital Eisenberg-Lerner, Adi Kimchi
May 26, 2009·Current Gastroenterology Reports·Sherry C Huang, Steven H Erdman
Nov 1, 2006·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Isabel Mérida, Antonia Avila-Flores
May 20, 2009·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M Sánchez-Céspedes
Apr 30, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Arshawn Sami, Michael Karsy
Jun 25, 2013·Cancer Letters·Zheng ShiJin-ku Bao
Mar 23, 2005·Current Opinion in Cell Biology·Dietmar E Martin, Michael N Hall
Jul 9, 2013·Neuroscience Letters·Theodore J Price, Gregory Dussor
Oct 1, 2013·Trends in Cell Biology·Sandro Goruppi, G Paolo Dotto
Feb 5, 2008·Expert Reviews in Molecular Medicine·Elias DrakosL Jeffrey Medeiros
Aug 10, 2010·Acta Pharmacologica Sinica·Bo LiuJin-Ming Yang
Nov 28, 2012·Acta Pharmacologica Sinica·Li-xia DongDian-sheng Zhong
Dec 3, 2010·Nature·Sushma GurumurthyNabeel Bardeesy
Feb 6, 2007·Nature Cell Biology·Emilie Vander HaarDo-Hyung Kim
Sep 5, 2007·Nature Clinical Practice. Gastroenterology & Hepatology·Kevin M Zbuk, Charis Eng
Dec 30, 2004·Nature Genetics·Ken InokiKun-Liang Guan
Aug 18, 2006·Nature Reviews. Cancer·David M Sabatini
Jul 25, 2009·Nature Reviews. Cancer·David B Shackelford, Reuben J Shaw
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini
Mar 4, 2008·Nature Reviews. Microbiology·Nicholas J BuchkovichJames C Alwine
Dec 21, 2004·Nature Structural & Molecular Biology·Michelle L HastingsAdrian R Krainer
Nov 26, 2008·Oncogene·A F Hezel, N Bardeesy
Nov 8, 2005·Cell Death and Differentiation·J H LeeJ Chung
Nov 17, 2005·Oncogene·David R Plas, Craig B Thompson
Jun 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·David B ShackelfordReuben J Shaw
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Arvind Ramanathan, Stuart L Schreiber
Dec 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sookhee BangSangwon F Kim
Jun 13, 2009·The Journal of Biological Chemistry·Jianrong WangTed Denmark
Sep 13, 2011·The Journal of Biological Chemistry·Carrie A StoltzmanDonald E Ayer
Mar 1, 2012·Critical Reviews in Food Science and Nutrition·Jia XuXiang-Hua Yan
Aug 18, 2010·Antioxidants & Redox Signaling·Eugenia MorselliGuido Kroemer
Jan 30, 2009·Carcinogenesis·Salvador Rodriguez-Nieto, Montse Sanchez-Cespedes
Dec 9, 2009·Carcinogenesis·Stephen D HurstingSusan N Perkins

❮ Previous
Next ❯

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