CRL4-DDB1-VPRBP ubiquitin ligase mediates the stress triggered proteolysis of Mcm10.

Nucleic Acids Research
Manpreet KaurSandeep Saxena

Abstract

When mammalian cells experience radiation insult, DNA replication is stalled to prevent erroneous DNA synthesis. UV-irradiation triggers proteolysis of Mcm10, an essential human replication factor, inhibiting the ongoing replication. Here, we report that Mcm10 associates with E3 ubiquitin ligase comprising DNA damage-binding protein, DDB1, cullin, Cul4 and ring finger protein, Roc1. Depletion of DDB1, Roc1 or Cul4 abrogates the UV-triggered Mcm10 proteolysis, implying that Cul4-Roc1-DDB1 ubiquitin ligase mediates Mcm10 downregulation. The purified Cul4-Roc1-DDB1 complex ubiquitinates Mcm10 in vitro, proving that Mcm10 is its substrate. By screening the known DDB1 interacting proteins, we discovered that VprBP is the substrate recognition subunit that targets Mcm10 for degradation. Hence, these results establish that Cul4-DDB1-VprBP ubiquitin ligase mediates the stress-induced proteolysis of replication factor, Mcm10.

References

Nov 26, 1999·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·N SekiT Saito
Sep 28, 2000·Cell·C A Joazeiro, A M Weissman
Oct 17, 2001·The Journal of Biological Chemistry·M IzumiF Hanaoka
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·V GopalakrishnanT J Kelly
Nov 14, 2001·The Journal of Biological Chemistry·Mitsuo WakasugiTsukasa Matsunaga
Jun 5, 2002·Annual Review of Biochemistry·Stephen P Bell, Anindya Dutta
Feb 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Joon-Kyu LeeJerard Hurwitz
Apr 23, 2004·The Journal of Biological Chemistry·Takeshi KondoMasahiro Asaka
Oct 21, 2004·Molecular Cell·Robin M Ricke, Anja-Katrin Bielinsky
Feb 3, 2005·Nature Reviews. Molecular Cell Biology·Matthew D Petroski, Raymond J Deshaies
Dec 20, 2005·Nature Cell Biology·Emily E Arias, Johannes C Walter
Jan 13, 2006·The Journal of Biological Chemistry·Takeshi SengaAnindya Dutta
Feb 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Maria G KapetanakiArthur S Levine
Apr 25, 2006·Nature Reviews. Cancer·Keiichi I Nakayama, Keiko Nakayama
May 6, 2006·The Journal of Biological Chemistry·Robin M Ricke, Anja-Katrin Bielinsky
Jun 20, 2006·Molecular and Cellular Biology·Sapna Das-BradooAnja-Katrin Bielinsky
Jul 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Lyubomir T VassilevLi Chen
Nov 7, 2006·Genes & Development·Christopher L SansamJacqueline A Lees
Dec 19, 2006·Cell Cycle·Jianqi CuiBassel E Sawaya
Feb 24, 2007·The Journal of Biological Chemistry·Sufang ZhangMarietta Y W T Lee
Jul 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kasia HreckaJacek Skowronski
Jul 17, 2007·PLoS Pathogens·Jean-Philippe BelzileEric A Cohen
Aug 7, 2007·Molecular Cell·Virginia AmadorMichele Pagano
Sep 8, 2007·EMBO Reports·Andrei L OkorokovGareth H Williams
Dec 11, 2007·The Journal of Biological Chemistry·Patrick D RobertsonBrandt F Eichman
Dec 27, 2008·Cell·Andrea ScrimaNicolas H Thomä
Mar 17, 2009·Nature Cell Biology·Subbareddy Maddika, Junjie Chen

❮ Previous
Next ❯

Citations

Apr 15, 2014·FEBS Letters·Jonathan Cooper, Filippo G Giancotti
Jan 22, 2013·Trends in Biochemical Sciences·Yee Mon Thu, Anja-Katrin Bielinsky
Oct 16, 2012·Current Opinion in Virology·Bizhan Romani, Eric A Cohen
Jan 6, 2016·Nature Communications·Zengli GuoYisong Y Wan
Feb 22, 2017·Genes·Ryan M Baxley, Anja-Katrin Bielinsky
Jan 13, 2018·Archives of Virology·Yanling YanRongge Yang
Apr 19, 2017·Molecular and Cellular Biology·Xianxi WangMichael J Emanuele
Dec 28, 2018·Journal of Molecular Cell Biology·N Max SchablaPatrick C Swanson
Mar 1, 2017·EMBO Reports·Delowar HossainWilliam Y Tsang
Jun 29, 2014·Nucleic Acids Research·Robert C AlverAnja-Katrin Bielinsky
Mar 30, 2018·Frontiers in Molecular Biosciences·Sang-Min JangMirit I Aladjem
Oct 3, 2020·Experimental & Molecular Medicine·Sang-Min JangMirit I Aladjem
Jan 25, 2020·Molecular Cell·Kurt M ReichermeierDonald S Kirkpatrick
Apr 16, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Sang-Min JangMirit I Aladjem

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
FACS
flow cytometry
transfection
PCR
immunoprecipitation
transfections
co-immunoprecipitation

Software Mentioned

FlowJo
Quantity One
Cell Quest Pro

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.