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A gene encoding a putative tyrosine phosphatase suppresses lethality of an N-end rule-dependent mutant

Ota, Irene M. and Varshavsky, Alexander (1992) A gene encoding a putative tyrosine phosphatase suppresses lethality of an N-end rule-dependent mutant. Proceedings of the National Academy of Sciences of the United States of America, 89 (6). pp. 2355-2359. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:OTApnas92

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Abstract

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In the yeast Saccharomyces cerevisiae, mutational inactivation of the N-end rule pathway is neither lethal nor phenotypically conspicuous. We have used a "synthetic lethal" screen to isolate a mutant that requires the N-end rule pathway for viability. An extragenic suppressor of this mutation was cloned and found to encode a 750-residue protein with strong sequence similarities to protein phosphotyrosine phosphatases. This heat-inducible gene was named PTP2. Null ptp2 mutants grow slowly, are hypersensitive to heat, and are viable in either the presence or absence of the N-end rule pathway. We discuss possible connections between dephosphorylation of phosphotyrosine in proteins and the N-end rule pathway of protein degradation.


Item Type:Article
Additional Information:Copyright © 1992 by the National Academy of Sciences. Communicated by Alexander Rich, October 18, 1991. We are indebted to M. Bernstein and A. Browne for technical assistance and to R. Baker, B. Bartel, J. Dohmen, K. Madura, E. Johnson, and N. Johnsson for discussions, advice, and comments on the manuscript. We also thank R. Baker for the gift of a Northern blot and B. Doran for secretarial assistance. This work was supported by grants to A.V. from the National Institutes of Health (DK39520 and GM31530). I.M.O. was supported by a postdoctoral fellowship from the Damon Runyon-Walter Winchell Cancer Fund. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Subject Keywords:YEAST, PROTEIN DEGRADATION, HEAT STRESS, UBIQUITIN, SHORT-LIVED PROTEIN, SACCHAROMYCES-CEREVISIAE, MOLECULAR-CLONING, ESCHERICHIA-COLI, SHUTTLE VECTORS, DEGRADATION, DNA, RECOGNITION, RESISTANCE
Record Number:CaltechAUTHORS:OTApnas92
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:OTApnas92
Alternative URL:http://www.pnas.org/cgi/content/abstract/89/6/2355
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1162
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:30 Dec 2005
Last Modified:14 Nov 2014 19:18

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