The unique N terminus of the UbcH10 E2 enzyme controls the threshold for APC activation and enhances checkpoint regulation of the APC.

Molecular Cell
Matthew K SummersPeter K Jackson

Abstract

In vitro, the anaphase-promoting complex (APC) E3 ligase functions with E2 ubiquitin-conjugating enzymes of the E2-C and Ubc4/5 families to ubiquitinate substrates. However, only the use of the E2-C family, notably UbcH10, is genetically well validated. Here, we biochemically demonstrate preferential use of UbcH10 by the APC, specified by the E2 core domain. Importantly, an additional E2-E3 interaction mediated by the N-terminal extension of UbcH10 regulates APC activity. Mutating the highly conserved N terminus increases substrate ubiquitination and the number of substrate lysines targeted, allows ubiquitination of APC substrates lacking their destruction boxes, increases resistance to the APC inhibitors Emi1 and BubR1 in vitro, and bypasses the spindle checkpoint in vivo. Fusion of the UbcH10 N terminus to UbcH5 restricts ubiquitination activity but does not direct specific interactions with the APC. Thus, UbcH10 combines a specific E2-E3 interface and regulation via its N-terminal extension to limit APC activity for substrate selection and checkpoint control.

References

Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·F M TownsleyJ V Ruderman
Nov 17, 1999·Molecular Biology of the Cell·H BastiansJ V Ruderman
Aug 2, 2000·Proceedings of the National Academy of Sciences of the United States of America·M GmachlJ M Peters
Apr 3, 2002·The Journal of Biological Chemistry·Yaqiong LinRavi Basavappa
Apr 19, 2002·Nature·Ning ZhengNikola P Pavletich
May 4, 2002·Nature Cell Biology·Jerry Y HsuPeter K Jackson
Jun 25, 2003·Molecular Cell·Matthew D Petroski, Raymond J Deshaies
Sep 6, 2003·Current Biology : CB·Hartmut C VodermaierJan-Michael Peters
Sep 14, 2004·Nature Structural & Molecular Biology·Danny T HuangBrenda A Schulman
Mar 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey J TungPeter K Jackson
Dec 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Engin OzkanJohann Deisenhofer
May 30, 2006·Nature Structural & Molecular Biology·Ali A Yunus, Christopher D Lima
Jun 27, 2006·Nature Cell Biology·Donald S KirkpatrickSteven P Gygi
Aug 10, 2006·Nature Reviews. Molecular Cell Biology·Jan-Michael Peters
Jan 16, 2007·Cell Cycle·Peter S Brzovic, Rachel E Klevit
Jan 16, 2007·Molecular and Cellular Neurosciences·Albert H Kim, Azad Bonni
Mar 16, 2007·Cell Cycle·David V HansenPeter K Jackson
Mar 21, 2007·Genes & Development·Janet L Burton, Mark J Solomon
Jul 17, 2007·Cell·Monica C Rodrigo-Brenni, David O Morgan
Jul 26, 2007·Cell Division·Laura A Díaz-Martínez, Hongtao Yu
Aug 1, 2007·The Journal of Cell Biology·Jamie M KeckSteven I Reed
Feb 12, 2008·Nature Structural & Molecular Biology·Danny T HuangBrenda A Schulman
Feb 22, 2008·The Journal of Biological Chemistry·Mark C HallHarry Charbonneau

❮ Previous
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Citations

Dec 16, 2011·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zhonglin HaoJohn Cowell
Nov 26, 2010·Quarterly Reviews of Biophysics·David Barford
Feb 22, 2011·Nature Cell Biology·Daisuke Izawa, Jonathon Pines
May 28, 2013·Nature Cell Biology·Weiping Wang, Marc W Kirschner
Oct 24, 2009·Nature Reviews. Molecular Cell Biology·Yihong Ye, Michael Rape
Jun 3, 2011·Nature Reviews. Molecular Cell Biology·Jonathon Pines
May 28, 2013·Nature Structural & Molecular Biology·Jeremiah J FryeBrenda A Schulman
Oct 14, 2009·Proceedings of the National Academy of Sciences of the United States of America·Adam WilliamsonMichael Rape
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Tao WuMarc W Kirschner
Mar 13, 2009·The Journal of Biological Chemistry·Markus A KleinschmidtStefan Gaubatz
Jun 6, 2009·Annual Review of Biochemistry·Raymond J Deshaies, Claudio A P Joazeiro
Feb 24, 2012·Journal of Cell Science·Annamaria Mocciaro, Michael Rape
Jan 24, 2014·PLoS Computational Biology·Aidan I BrownAndrew D Rutenberg
Dec 24, 2013·The International Journal of Biochemistry & Cell Biology·Chanlu XieQihan Dong
Apr 29, 2014·Nature Communications·Kosuke SakoNoriyuki Sagata
Jun 7, 2011·Oncogene·S GiovinazziA M Ishov
Apr 23, 2013·The Journal of Biological Chemistry·Feroz SarkariYi Sheng
Jul 4, 2012·Cellular and Molecular Life Sciences : CMLS·Kozo Tanaka
Jan 13, 2010·The Journal of Cell Biology·Janine H van ReeJan M van Deursen
Apr 17, 2013·The Journal of Cell Biology·Ivana Primorac, Andrea Musacchio
Oct 11, 2011·Critical Reviews in Biochemistry and Molecular Biology·Harish N Ramanathan, Yihong Ye
Jan 26, 2011·Critical Reviews in Biochemistry and Molecular Biology·Janel R McLeanKathleen L Gould
Apr 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Nicholas G BrownBrenda A Schulman
May 12, 2015·Journal of Molecular Biology·Prerana Agarwal BankaAjit B Datta
Oct 8, 2011·Trends in Cell Biology·Katherine E WickliffeMichael Rape
Jun 7, 2011·Trends in Biochemical Sciences·Anja Bremm, David Komander
Aug 20, 2009·Molecular Systems Biology·Sjoerd J L van WijkH Th Marc Timmers
Jan 29, 2013·The Plant Journal : for Cell and Molecular Biology·Qingzhen ZhaoQi Xie
Sep 21, 2011·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Surinder M Soond, Andrew Chantry
Mar 24, 2016·Cell Research·Mikaela D StewartPeter S Brzovic
Apr 29, 2015·Molecular Carcinogenesis·Nunzio Antonio CacciolaPierlorenzo Pallante
Sep 12, 2015·Science Translational Medicine·Monica VenereJeremy N Rich
Dec 17, 2010·The Biochemical Journal·Dawn M WenzelRachel E Klevit
Jul 31, 2013·Current Opinion in Cell Biology·Allison Craney, Michael Rape
Apr 23, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ya-Lin HuangChristof Niehrs

❮ Previous
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