A gene encoding a putative tyrosine phosphatase suppresses lethality of an N-end rule-dependent mutant.
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.
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Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Varshavsky
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D004271:DNA, Fungal / Q000235:genetics / Q000302:isolation & purification; D004330:Drosophila / Q000235:genetics; D005800:Genes, Fungal; D005804:Genes, Lethal; D005838:Genotype; D006358:Hot Temperature; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012331:RNA, Fungal / Q000235:genetics / Q000302:isolation & purification; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013489:Suppression, Genetic; D016385:TATA Box
D004271:DNA, Fungal; D012331:RNA, Fungal; D017027:Protein Tyrosine Phosphatases