Feedback regulation of Ras signaling by Rabex-5-mediated ubiquitination.

Current Biology : CB
L XuDafna Bar-Sagi

Abstract

Ras proteins play a central role in transducing signals that control cell proliferation, differentiation, motility, and survival. The location-specific signaling activity of Ras has been previously shown to be regulated by ubiquitination [1]. However, the molecular machinery that controls Ras ubiquitination has not been defined. Here we demonstrate through biochemical and functional analyses that Rabex-5 (also known as RabGEF1) [2, 3] functions as an E3 ligase for Ras. Rabex-5-mediated Ras ubiquitination promotes Ras endosomal localization and leads to the suppression of ERK activation. Moreover, the Ras effector RIN1 [4, 5] is required for Rabex-5-dependent Ras ubiquitination, suggesting a feedback mechanism by which Ras activation can be coupled to ubiquitination. These findings define new elements in the regulatory circuitry that link Ras compartmentalization to signaling output.

References

May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·L HanJ Colicelli
May 4, 2002·Nature Cell Biology·Vi K ChiuMark R Philips
May 3, 2003·Nature Reviews. Molecular Cell Biology·John F Hancock
Jul 6, 2004·Nature Immunology·See-Ying TamStephen J Galli
Feb 12, 2005·Science·Oliver RocksPhilippe I H Bastiaens
Jul 20, 2005·The Journal of Cell Biology·J Shawn GoodwinAnne K Kenworthy
Aug 3, 2005·Nature Reviews. Molecular Cell Biology·Rebecca L WelchmanR John Mayer
Sep 9, 2005·The EMBO Journal·Kaisa Haglund, Ivan Dikic
Dec 7, 2005·Trends in Cell Biology·Darren S CarneyBruce F Horazdovsky
Feb 8, 2006·Nature Structural & Molecular Biology·Sangho LeeJames H Hurley
Mar 2, 2006·Molecular Cell·Natalia JuraDafna Bar-Sagi
Mar 23, 2006·Annual Review of Immunology·Adam Mor, Mark R Philips
Aug 19, 2007·Molecular Biology of the Cell·Huaiping ZhuGuangpu Li

❮ Previous
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Citations

Dec 23, 2011·Nature Reviews. Molecular Cell Biology·Ian M AhearnMark R Philips
Aug 2, 2013·Cell Communication and Signaling : CCS·Lan K NguyenBoris N Kholodenko
Nov 28, 2012·PloS One·Christine JansonJohn Colicelli
Jun 25, 2014·ELife·Zhe ZhangJianping Ding
Oct 30, 2015·Proceedings of the National Academy of Sciences of the United States of America·Linda FabrisGustavo Baldassarre
Jun 21, 2014·Small GTPases·Véronik LachanceJean-Luc Parent
Jun 19, 2015·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Tadashi Nakagawa, Keiko Nakayama
Sep 27, 2012·Expert Opinion on Therapeutic Patents·Elena SaccoMarco Vanoni
Dec 7, 2011·Small GTPases·Michelle de la VegaJames A Johnston
Jun 28, 2012·Small GTPases·Ze-Yi ZhengEric C Chang
Jul 22, 2011·Small GTPases·Tomohiko Taguchi, Ryo Misaki
Aug 10, 2010·Current Biology : CB·John Colicelli
Sep 15, 2012·Developmental Cell·Michael J ClagueSylvie Urbé
Apr 22, 2014·Cell Reports·Taoling ZengHong-Rui Wang
Jun 19, 2012·Biochemical and Biophysical Research Communications·Donghyuk ShinSangho Lee
Mar 1, 2012·Biochemical and Biophysical Research Communications·Hoon ChoiSangho Lee
Sep 8, 2016·Proceedings of the National Academy of Sciences of the United States of America·David MillrineTadamitsu Kishimoto
Nov 15, 2014·Cells·Zoi ErpapazoglouRosine Haguenauer-Tsapis
Sep 20, 2018·The Journal of Biological Chemistry·Byeong Hyeok ChoiWei Dai
Nov 7, 2014·Nature Medicine·Doris PopovicIvan Dikic
Apr 21, 2011·Nature Reviews. Neuroscience·Hiroshi Kawabe, Nils Brose
Dec 16, 2017·Nature Reviews. Cancer·Daniela SenftZe'ev A Ronai
Feb 3, 2012·Physiological Reviews·Sara SigismundPier Paolo Di Fiore
Feb 18, 2016·EMBO Molecular Medicine·Maria Francesca BaiettiAnna A Sablina
May 23, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pamela Y TingJohn Colicelli
Feb 13, 2018·Oncotarget·Byeong Hyeok ChoiWei Dai
May 19, 2011·The Journal of Biological Chemistry·Hiroaki KajihoToshiaki Katada
Jun 20, 2020·PLoS Genetics·Chalita WashingtonCathie M Pfleger
Dec 18, 2013·The Journal of Biological Chemistry·Kazutaka SumitaAtsuo T Sasaki
Apr 9, 2016·Small GTPases·Gustavo Baldassarre, Barbara Belletti
Feb 17, 2017·Molecular & Cellular Oncology·Barbara BellettiGustavo Baldassarre
Dec 3, 2016·Biochemical Society Transactions·Ana HerreroWalter Kolch
Aug 18, 2017·BMC Biophysics·H Billur EnginHannah Carter
Jan 10, 2018·Cold Spring Harbor Perspectives in Medicine·Ian AhearnMark R Philips
Oct 28, 2019·The Journal of Biological Chemistry·Henrik G Dohlman, Sharon L Campbell

❮ Previous
Next ❯

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