Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling.

PloS One
Wei LiClaudio A P Joazeiro

Abstract

Specificity of protein ubiquitylation is conferred by E3 ubiquitin (Ub) ligases. We have annotated approximately 617 putative E3s and substrate-recognition subunits of E3 complexes encoded in the human genome. The limited knowledge of the function of members of the large E3 superfamily prompted us to generate genome-wide E3 cDNA and RNAi expression libraries designed for functional screening. An imaging-based screen using these libraries to identify E3s that regulate mitochondrial dynamics uncovered MULAN/FLJ12875, a RING finger protein whose ectopic expression and knockdown both interfered with mitochondrial trafficking and morphology. We found that MULAN is a mitochondrial protein - two transmembrane domains mediate its localization to the organelle's outer membrane. MULAN is oriented such that its E3-active, C-terminal RING finger is exposed to the cytosol, where it has access to other components of the Ub system. Both an intact RING finger and the correct subcellular localization were required for regulation of mitochondrial dynamics, suggesting that MULAN's downstream effectors are proteins that are either integral to, or associated with, mitochondria and that become modified with Ub. Interestingly, MULAN had previously be...Continue Reading

References

Jun 15, 1999·The Journal of Cell Biology·H A Fisk, M P Yaffe
Aug 10, 2000·Trends in Cell Biology·S Desagher, J C Martinou
Sep 28, 2000·Cell·C A Joazeiro, A M Weissman
May 2, 2001·The EMBO Journal·A ReymondA Ballabio
Aug 22, 2001·Molecular Biology of the Cell·E SmirnovaA M van der Bliek
Aug 29, 2002·The EMBO Journal·Quan ZhaoNicholas J Hoogenraad
Nov 15, 2002·The Journal of Biological Chemistry·Yan XiaTony Hunter
Jun 17, 2003·Molecular Biology of the Cell·Stefan FritzBenedikt Westermann
Aug 15, 2003·The Journal of Biological Chemistry·Thomas WaizeneggerDoron Rapaport
Feb 20, 2004·Current Biology : CB·Zdena HarderHeidi McBride
May 21, 2004·Physiological Genomics·Ignacio MarínAlberto Ferrús
Nov 3, 2004·Genes & Development·Jianping JinJ Wade Harper
Dec 2, 2004·Biochimica Et Biophysica Acta·Cecile M Pickart, Michael J Eddins
Dec 16, 2004·Molecular & Cellular Proteomics : MCP·Karim RezaulDavid Han
Feb 3, 2005·Nature Reviews. Molecular Cell Biology·Matthew D Petroski, Raymond J Deshaies
May 10, 2005·Human Mutation·Jacques S BeckmannLaurent Falquet
Oct 7, 2005·Genome Biology·Peter J StogiosGilbert G Privé
Oct 21, 2005·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Germana Meroni, Graciana Diez-Roux
Nov 9, 2005·Methods in Enzymology·Wei LiClaudio A P Joazeiro
Nov 16, 2005·Annual Review of Genetics·Koji Okamoto, Janet M Shaw
Nov 25, 2005·Journal of Cell Science·Peter J Hollenbeck, William M Saxton
Jan 26, 2006·The Journal of Biological Chemistry·Kieran M Short, Timothy C Cox
Jul 29, 2006·The EMBO Journal·Ryo YonashiroShigeru Yanagi
Oct 13, 2006·Nature·Mariusz KarbowskiRichard J Youle
Nov 23, 2006·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Roberto Perez-TorradoPierre-Antoine Defossez
Mar 21, 2007·Genome Biology·Birgit EisenhaberMarie-Theres Hauser
Jun 15, 2007·Critical Reviews in Biochemistry and Molecular Biology·Mirko Koppen, Thomas Langer
Jul 4, 2007·The Journal of Cell Biology·Mariusz KarbowskiRichard J Youle

❮ Previous
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Citations

Jul 27, 2010·Asian Journal of Andrology·Yun-Qiang LiuSi-Zhong Zhang
Apr 5, 2014·Nature Structural & Molecular Biology·Christopher E Berndsen, Cynthia Wolberger
Apr 16, 2014·Journal of Bioenergetics and Biomembranes·Taylor A MattoxMonte S Willis
Jun 25, 2014·The Journal of Cell Biology·Jessica M BonamePaul J Lehner
Mar 21, 2013·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Zengrong LiXiangyang Zou
Jan 6, 2010·EMBO Molecular Medicine·Emma DeasNicholas W Wood
Oct 30, 2013·Oncogene·S-M HedeF J Swartling
Oct 4, 2014·BMC Genomics·Matthew J Edmonds, Alan Morgan
Mar 21, 2008·Molecular Biology of the Cell·Mickael M J CohenAllan M Weissman
Aug 5, 2008·BMC Evolutionary Biology·Marco SardielloGermana Meroni
Aug 19, 2009·Molecular and Cellular Biology·Harald W PlattaRalf Erdmann
Dec 17, 2009·The Journal of Biological Chemistry·Renuka K PandyaHidde L Ploegh
Apr 2, 2010·American Journal of Physiology. Cell Physiology·Roberta A Gottlieb, Raquel S Carreira
Apr 7, 2010·Annual Review of Biochemistry·Stephanie MohrNorbert Perrimon
Apr 20, 2010·Expert Reviews in Molecular Medicine·Inês Pimenta de CastroRoberta Tufi
Oct 20, 2010·Molecular & Cellular Proteomics : MCP·Christian M LochJames E Strickler
Dec 2, 2010·The Journal of Biological Chemistry·Debra WyattAdriano Marchese
Dec 7, 2010·Antioxidants & Redox Signaling·Gilad Twig, Orian S Shirihai
Mar 31, 2011·Nature Reviews. Molecular Cell Biology·Caroline GrabbeIvan Dikic
May 11, 2011·Genome Biology·Antonio SarikasZhen-Qiang Pan
May 11, 2011·BMC Proceedings·Trafina S JadhavMichael C Wooten
Mar 14, 2012·Cell Research·Seunghee BaeSungkwan An
Feb 9, 2013·Molecular Biology and Evolution·Andrew Paul HutchinsDiego Miranda-Saavedra
Mar 19, 2013·PLoS Computational Biology·Jonathan WoodsmithUlrich Stelzl
Jun 27, 2013·BMC Biology·Sonja LorenzJohn Kuriyan
Apr 27, 2010·Journal of Biochemistry·Yoko Kimura, Keiji Tanaka
Jun 26, 2010·Cellular and Molecular Life Sciences : CMLS·Dong-Hyung ChoStuart A Lipton
Mar 3, 2012·Cellular and Molecular Life Sciences : CMLS·Márcio S BaptistaPatrícia Maciel
Feb 15, 2011·Antioxidants & Redox Signaling·Franziska KriegenburgRasmus Hartmann-Petersen
Aug 31, 2013·Neuromolecular Medicine·Mathias DroescherAndrea Pichler

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Methods Mentioned

BETA
transfection
transfections
PCR
confocal microscopy
electron microscopy
FCS

Software Mentioned

Celera
MULAN
Homologene
BLAST
Genscan
HMMER
Ensembl

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