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Verma R, et al.  (2011) Cdc48/p97 mediates UV-dependent turnover of RNA Pol II. Mol Cell 41(1):82-92

Abstract: 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.CI - Copyright A(c) 2011 Elsevier Inc. All rights reserved.

Status: Published Type: Journal Article | Research Support, Non-U.S. Gov't PubMed ID: 21211725

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Topics Genes linked to topics (#1 - 10 )
CDC34 CDC48 CUL3 MAD2 RAD26 RPO21 RSP5 SHP1 UBX2 UBX3
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Topics Genes linked to topics (#11 - 14 )
UBX4 UBX5 UBX6 UBX7
Additional Literature blue ball blue ball
Genetic Interactions blue ball blue ball
Mutants/Phenotypes blue ball blue ball blue ball blue ball
Primary Literature blue ball blue ball
Protein-protein Interactions blue ball
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