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

A gene encoding a putative tyrosine phosphatase suppresses lethality of an N-end rule-dependent mutant.
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编码推定酪氨酸磷酸酶的基因抑制 N 端规则依赖性突变体的致死率。

DOI:
10.1073/pnas.89.6.2355
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发表时间:
1992
影响因子:
11.1
通讯作者:
Varshavsky,A
Varshavsky,A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ota,IM;Varshavsky,A

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N 端规则将蛋白质的体内半衰期与其 N 端残基的身份联系起来。在酿酒酵母中,N 端规则途径的突变失活既不致死,也不在表型上引人注目。我们使用“合成致死”筛选来分离需要 N 端规则途径才能生存的突变体。克隆了该突变的基因外抑制子,发现它编码一个 750 个残基的蛋白质,该蛋白质与蛋白质磷酸酪氨酸磷酸酶具有很强的序列相似性。这个热诱导基因被命名为PTP2。无效 ptp2 突变体生长缓慢,对热过敏,并且在存在或不存在 N 端规则途径的情况下均可存活。我们讨论了蛋白质中磷酸酪氨酸的去磷酸化与蛋白质降解的 N 端规则途径之间可能的联系。
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.