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The TFIIH Subunit Tfb3 Regulates Cullin Neddylation

Rabut, Gwenaël and Le Dez, Gaëlle and Verma, Rati and Makhnevych, Taras and Knebel, Axel and Kurz, Thimo and Boone, Charles and Deshaies, Raymond J. and Peter, Matthias (2011) The TFIIH Subunit Tfb3 Regulates Cullin Neddylation. Molecular Cell, 43 (3). pp. 488-495. ISSN 1097-2765. PMCID PMC3186349. http://resolver.caltech.edu/CaltechAUTHORS:20110830-133501205

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Abstract

Cullin proteins are scaffolds for the assembly of multisubunit ubiquitin ligases, which ubiquitylate a large number of proteins involved in widely varying cellular functions. Multiple mechanisms cooperate to regulate cullin activity, including neddylation of their C-terminal domain. Interestingly, we found that the yeast Cul4-type cullin Rtt101 is not only neddylated but also ubiquitylated, and both modifications promote Rtt101 function in vivo. Surprisingly, proper modification of Rtt101 neither correlated with catalytic activity of the RING domain of Hrt1 nor required the Nedd8 ligase Dcn1. Instead, ubiquitylation of Rtt101 was dependent on the ubiquitin-conjugating enzyme Ubc4, while efficient neddylation involves the RING domain protein Tfb3, a subunit of the transcription factor TFIIH. Tfb3 also controls Cul3 neddylation and activity in vivo, and physically interacts with Ubc4 and the Nedd8-conjugating enzyme Ubc12 and the Hrt1/Rtt101 complex. Together, these results suggest that the conserved RING domain protein Tfb3 controls activation of a subset of cullins.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.molcel.2011.05.032DOIArticle
http://www.sciencedirect.com/science/article/pii/S1097276511004576PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186349/PubMed CentralArticle
http://www.sciencedirect.com/science/MiamiMultiMediaURL/1-s2.0-S1097276511004576/1-s2.0-S1097276511004576-mmc1.pdf/272198/html/S1097276511004576/839cc3e4c458ef6b3cfb29075b83baff/mmc1.pdfPublisherSupplemental Information
ORCID:
AuthorORCID
Deshaies, Raymond J.0000-0002-3671-9354
Additional Information:© 2011 Elsevier Inc. Received 1 December 2010; revised 4 April 2011; accepted 16 May 2011. Published: August 4, 2011. Available online 4 August 2011. We thank C. Rupp, C. Zbinden and R. Oania for technical assistance, and B. Schulman and members of the Peter laboratory for helpful discussions. G. Rabut was recipient of a Human Frontier Science Program Long-Term fellowship and is currently supported by INSERM and Région Bretagne. Work in the Deshaies and Peter laboratories is supported by the Howard Hughes Medical Institute and by research grants from Oncosuisse, the Swiss National Science Foundation, and the ETH Zurich, respectively.
Funders:
Funding AgencyGrant Number
Institut national de la santé et de la recherche médicale (INSERM)UNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Oncosuisse TrustUNSPECIFIED
Swiss National Science Foundation (SNSF)UNSPECIFIED
ETH Zurich UNSPECIFIED
Region BretagneUNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
PubMed Central ID:PMC3186349
Record Number:CaltechAUTHORS:20110830-133501205
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20110830-133501205
Official Citation:Gwenael Rabut, Gaelle Le Dez, Rati Verma, Taras Makhnevych, Axel Knebel, Thimo Kurz, Charles Boone, Raymond J. Deshaies, Matthias Peter, The TFIIH Subunit Tfb3 Regulates Cullin Neddylation, Molecular Cell, Volume 43, Issue 3, 5 August 2011, Pages 488-495, ISSN 1097-2765, DOI: 10.1016/j.molcel.2011.05.032. (http://www.sciencedirect.com/science/article/pii/S1097276511004576)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:25167
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:30 Aug 2011 21:04
Last Modified:29 Apr 2019 21:44

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