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Cdc48/p97 Mediates UV-Dependent Turnover of RNA Pol II

Verma, Rati and Oania, Robert and Fang, Ruihua and Smith, Geoffrey T. and Deshaies, Raymond J. (2011) Cdc48/p97 Mediates UV-Dependent Turnover of RNA Pol II. Molecular Cell, 41 (1). pp. 82-92. ISSN 1097-2765. PMCID PMC3063307.

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Cdc48/p97 is an essential ATPase whose role in targeting substrates to the ubiquitin-proteasome system (UPS) remains unclear. Existing models posit that Cdc48 acts upstream of UPS receptors. To address this hypothesis, we examined the association of ubiquitin (Ub) conjugates with 26S proteasomes. Unexpectedly, proteasomes isolated from cdc48 mutants contain high levels of Ub conjugates, and mass spectrometry identified numerous nonproteasomal proteins, including Rpb1, the largest subunit of RNA Pol II. UV-induced turnover of Rpb1 depends upon Cdc48-Ufd1-Npl4, Ubx4, and the uncharacterized adaptor Ubx5. Ubiquitinated Rpb1, proteasomes, and Cdc48 accumulate on chromatin in UV-treated wild-type cells, and the former two accumulate to higher levels in mutant cells, suggesting that degradation of Rpb1 is facilitated by Cdc48 at sites of stalled transcription. These data reveal an intimate coupling of function between proteasomes and Cdc48 that we suggest is necessary to sustain processive degradation of unstable subunits of some macromolecular protein complexes.

Item Type:Article
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URLURL TypeDescription CentralArticle Information
Deshaies, Raymond J.0000-0002-3671-9354
Additional Information:© 2011 Elsevier. Received 4 June 2010; revised 9 October 2010; accepted 10 December 2010. Published: January 6, 2011. Available online 11 January 2011. We thank D.G. Drubin, G. Hartzog, M. Hochstrasser, J. Huibregtse, E. Johnson, D. Kellogg, T. Miyakawa, Y. Saeki, W. Seufert, P. Silver, T. Sommer, A. Toh-E, A. Varshavsky, F. Winston, and Y. Ye for yeast strains, expression plasmids, and antibodies. We thank the members of the Deshaies lab for helpful discussions. R.J.D. is an Investigator of the Howard Hughes Medical Institute, which supported this work.
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Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:1
PubMed Central ID:PMC3063307
Record Number:CaltechAUTHORS:20110202-104707165
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Official Citation:Rati Verma, Robert Oania, Ruihua Fang, Geoffrey T. Smith, Raymond J. Deshaies, Cdc48/p97 Mediates UV-Dependent Turnover of RNA Pol II, Molecular Cell, Volume 41, Issue 1, 7 January 2011, Pages 82-92, ISSN 1097-2765, DOI: 10.1016/j.molcel.2010.12.017.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:21965
Deposited By: Tony Diaz
Deposited On:08 Feb 2011 03:53
Last Modified:03 Oct 2019 02:32

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