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Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85

Finley, Daniel and Ciechanover, Aaron and Varshavsky, Alexander (1984) Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85. Cell, 37 (1). pp. 43-55. ISSN 0092-8674. doi:10.1016/0092-8674(84)90299-x.

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Ubiquitin, a 76 residue protein, occurs in eucaryotic cells either free or covalently joined to a variety of protein species. Previous work suggested that ubiquitin may function as a signal for attack by proteinases specific for ubiquitin-protein conjugates. We show that the mouse cell line ts85, a previously isolated cell cycle mutant, is temperature-sensitive in ubiquitin-protein conjugation, and that this effect is due to the specific thermolability of the ts85 ubiquitin-activating enzyme (E1). From E1 thermoinactivation kinetics in mixed (wild-type plus ts85) extracts, and from copurification of the determinant of E1 thermolability with E1 in ubiquitin-affinity chromatography, we conclude that the determinant of E1 thermolability is contained within the E1 polypeptide. ts85 cells fail to degrade otherwise short-lived intracellular proteins at the nonpermissive temperature (accompanying paper), demonstrating that degradation of the bulk of short-lived proteins in this higher eucaryotic cell proceeds through a ubiquitin-dependent pathway. We discuss possible roles of ubiquitin-dependent pathways in DNA transactions, the cell cycle, and the heat shock response.

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Varshavsky, Alexander0000-0002-4011-258X
Additional Information:© 1984 by MIT. Received 21 December 1983, Revised 2 March 1984. We are greatly indebted to Hideo Yasuda (University of California, Davis) for providing us with the ts85, ts85R-MN3, and FM3A cells. The modified procedure used for silver staining was developed by Francois Strauss. We thank Mark Solomon, Paul Swerdlow, and especially Joan Park for helpful comments on the manuscript. This work was supported by grants to A. V. from the National Institute of General Medical Sciences (GM31530) and the National Cancer Institute (CA30367). D. F. was supported by a departmental training grant from the National Institutes of Health. A. C. was supported by the Melvin Brown Memorial Foundation through the Israel Cancer Research Fund and by fellowships from the Leukemia Society of America and the Medical Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. Thus article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate thus fact.
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NIH Predoctoral FellowshipUNSPECIFIED
Melvin Brown Memorial FoundationUNSPECIFIED
Israel Cancer Research FundUNSPECIFIED
Leukemia Society of AmericaUNSPECIFIED
Medical FoundationUNSPECIFIED
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Official Citation:Daniel Finley, Aaron Ciechanover, Alexander Varshavsky, Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85, Cell, Volume 37, Issue 1, 1984, Pages 43-55, ISSN 0092-8674,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107690
Deposited By: George Porter
Deposited On:25 Jan 2021 15:29
Last Modified:16 Nov 2021 19:05

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