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UFD4 lacking the proteasome-binding region catalyses ubiquitination but is impaired in proteolysis

Xie, Youming and Varshavsky, Alexander (2002) UFD4 lacking the proteasome-binding region catalyses ubiquitination but is impaired in proteolysis. Nature Cell Biology, 4 (12). pp. 1003-1007. ISSN 1465-7392. doi:10.1038/ncb889.

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The ubiquitin system recognizes degradation signals of protein substrates through E3–E2 ubiquitin ligases, which produce a substrate-linked multi-ubiquitin chain. Ubiquitinated substrates are degraded by the 26S proteasome, which consists of the 20S protease and two 19S particles. We previously showed that UBR1 and UFD4, two E3 ligases of the yeast Saccharomyces cerevisiae, interact with specific proteasomal subunits. Here we advance this analysis for UFD4 and show that it interacts with RPT4 and RPT6, two subunits of the 19S particle. The 201-residue amino-terminal region of UFD4 is essential for its binding to RPT4 and RPT6. UFD4 ΔN, which lacks this N-terminal region, adds ubiquitin to test substrates with apparently wild-type activity, but is impaired in conferring short half-lives on these substrates. We propose that interaction of a targeted substrate with the 26S proteasome involves contacts of specific proteasomal subunits with the substrate-bound ubiquitin ligase, with the substrate-linked multi-ubiquitin chain and with the substrate itself. This multiple-site binding may function to slow down dissociation of the substrate from the proteasome and to facilitate the unfolding of substrate through ATP-dependent movements of the chaperone subunits of the 19S particle.

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Varshavsky, Alexander0000-0002-4011-258X
Additional Information:© 2002 Nature Publishing Group. Received 23 July 2002, Revised 5 October 2002, Accepted 22 October 2002, Published 25 November 2002. We thank R. Verma and R. Deshaies for the purified 26S proteasome; E. Johnson, D. Botstein and S. Jentsch for S. cerevisiae strains and plasmids; and members of the Varshavsky laboratory, particularly R. Hu and J. Sheng, for assistance and advice. This work was supported by a grant to A.V. from the NIH. Y.X. was supported in part by a postdoctoral fellowship from the NIH.
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NIH Postdoctoral FellowshipUNSPECIFIED
Issue or Number:12
Record Number:CaltechAUTHORS:20150325-152811477
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56089
Deposited By: Tony Diaz
Deposited On:26 Mar 2015 02:39
Last Modified:10 Nov 2021 20:54

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