RNF4-mediated polyubiquitination regulates the Fanconi anemia/BRCA pathway

The Journal of Clinical Investigation
Jenny XieAlan D D'Andrea

Abstract

The Fanconi anemia/BRCA (FA/BRCA) pathway is a DNA repair pathway that is required for excision of DNA interstrand cross-links. The 17 known FA proteins, along with several FA-associated proteins (FAAPs), cooperate in this pathway to detect, unhook, and excise DNA cross-links and to subsequently repair the double-strand breaks generated in the process. In the current study, we identified a patient with FA with a point mutation in FANCA, which encodes a mutant FANCA protein (FANCAI939S). FANCAI939S failed to bind to the FAAP20 subunit of the FA core complex, leading to decreased stability. Loss of FAAP20 binding exposed a SUMOylation site on FANCA at amino acid residue K921, resulting in E2 SUMO-conjugating enzyme UBC9-mediated SUMOylation, RING finger protein 4-mediated (RNF4-mediated) polyubiquitination, and proteasome-mediated degradation of FANCA. Mutation of the SUMOylation site of FANCA rescued the expression of the mutant protein. Wild-type FANCA was also subject to SUMOylation, RNF4-mediated polyubiquitination, and degradation, suggesting that regulated release of FAAP20 from FANCA is a critical step in the normal FA pathway. Consistent with this model, cells lacking RNF4 exhibited interstrand cross-linker hypersensitivi...Continue Reading

References

Dec 16, 1997·Proceedings of the National Academy of Sciences of the United States of America·O LevranA D Auerbach
Jun 22, 1999·Molecular and Cellular Biology·I Garcia-HigueraA D D'Andrea
Dec 2, 2004·Molecular and Cellular Biology·Masamichi IshiaiMinoru Takata
Nov 16, 2006·PLoS Biology·Hiroshi ArakawaJean-Marie Buerstedde
Sep 1, 2007·The EMBO Journal·John PruddenMichael N Boddy
Oct 11, 2007·Human Mutation·Najim AmezianeHans Joenje
Apr 15, 2008·Nature Cell Biology·Michael H TathamRonald T Hay
May 28, 2009·Science Signaling·Filip GolebiowskiRonald T Hay
Feb 5, 2010·Cancer Cell·Jiri Bartek, Zdenek Hodny
Jan 18, 2011·Nature Genetics·Yonghwan KimAgata Smogorzewska
Mar 30, 2011·Molecular and Cellular Biology·John PruddenMichael N Boddy
Apr 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kimiyo N YamamotoKouji Hirota
Jun 15, 2011·FEBS Letters·Simon Bekker-Jensen, Niels Mailand
Jul 8, 2011·Nature·Frédéric LangevinKetan J Patel
Jan 24, 2012·Nature Structural & Molecular Biology·Hyungjin KimAlan D D'Andrea
Mar 8, 2012·Proceedings of the National Academy of Sciences of the United States of America·Justin Wai Chung LeungJunjie Chen
May 29, 2012·The EMBO Journal·Kuntian LuoZhenkun Lou
Jun 5, 2012·Genes & Development·Yaron GalantyStephen P Jackson
Jul 4, 2012·Genes & Development·Hyungjin Kim, Alan D D'Andrea
Dec 1, 2012·Cell Death and Differentiation·R VyasJ-C Marine
Jan 18, 2013·Nature·Molly C Kottemann, Agata Smogorzewska
Feb 19, 2013·Molecular Cell·Stephen P Jackson, Daniel Durocher
Mar 22, 2013·Biochemical Society Transactions·Ronald T Hay
Apr 30, 2013·Médecine sciences : M/S·Frédéric P M LangevinKetan J Patel
Sep 11, 2013·Annual Review of Genetics·Stefan Jentsch, Ivan Psakhye
Apr 10, 2014·EMBO Reports·Lynda M GroocockMichael N Boddy
Jun 7, 2014·Molecular Cell·Eeson RajendraLori A Passmore
Sep 11, 2014·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kouji HirotaShunichi Takeda

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Citations

Jul 22, 2015·Molecules and Cells·Ukhyun Jo, Hyungjin Kim
May 6, 2016·Frontiers in Genetics·Kate E Coleman, Tony T Huang
Apr 21, 2016·Cellular and Molecular Life Sciences : CMLS·David Lopez-MartinezMartin A Cohn
Aug 21, 2016·Mutation Research. Reviews in Mutation Research·Xavier RenaudinFilippo Rosselli
May 18, 2016·Scientific Reports·Jean-François MaureRonald T Hay
May 19, 2017·The Journal of Biological Chemistry·Nozomi TomimatsuSandeep Burma
Apr 11, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Luxiang WangJun Zhu
Jan 30, 2018·Nature Reviews. Cancer·Grzegorz Nalepa, D Wade Clapp
Oct 1, 2019·Proteomics·Ramesh Kumar, Kanaga Sabapathy
Nov 2, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yiwei XiongHebin Liu
Jan 27, 2020·Environmental and Molecular Mutagenesis·Julie Rageul, Hyungjin Kim
Aug 9, 2020·The Journal of Biological Chemistry·Bhavika NagareddyHyungjin Kim
Jan 7, 2020·Mini Reviews in Medicinal Chemistry·Kajal GhosalSudit Mukherjee
Aug 14, 2019·International Journal of Molecular Sciences·Mathias BoulangerGuillaume Bossis
Apr 5, 2018·Journal of Developmental Biology·Mona AbedAmir Orian
Jan 31, 2020·Frontiers in Cell and Developmental Biology·Jan Keiten-SchmitzStefan Müller
Jul 22, 2019·DNA Repair·Julie RageulHyungjin Kim
Feb 22, 2017·Cell·Georgios I KarrasSusan Lindquist
Jun 3, 2021·International Journal of Molecular Sciences·Ya-Chu ChangAnja-Katrin Bielinsky
Jan 29, 2020·Chemical Research in Toxicology·Lok Ming TamYinsheng Wang
Mar 16, 2017·Science Signaling·Bálint MészárosZsuzsanna Dosztányi
Dec 7, 2021·Frontiers in Genetics·Nathan EllisMichael J Matunis

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Datasets Mentioned

BETA
GM6914
GM0637

Methods Mentioned

BETA
coimmunoprecipitation
pull down
transfection
immunoprecipitation
pull-down

Software Mentioned

AxioVision
CellTiterGlo

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