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Published January 7, 2011 | Supplemental Material + Accepted Version
Journal Article Open

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


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.

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.

Attached Files

Accepted Version - nihms264976.pdf

Supplemental Material - mmc1.pdf


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