NPI1, AN ESSENTIAL YEAST GENE INVOLVED IN INDUCED DEGRADATION OF GAP1 AND FUR4 PERMEASES, ENCODES THE RSP5 UBIQUITIN-PROTEIN LIGASE

NPI1, AN ESSENTIAL YEAST GENE INVOLVED IN INDUCED DEGRADATION OF GAP1 AND FUR4 PERMEASES, ENCODES THE RSP5 UBIQUITIN-PROTEIN LIGASE
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DOI:
10.1111/j.1365-2958.1995.mmi_18010077.x
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发表时间:
1995-10-01
影响因子:
3.6
通讯作者:
ANDRE, B
ANDRE, B
中科院分区:
生物学2区
文献类型:
--
作者:
HEIN, C;SPRINGAEL, JY;ANDRE, B

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当酵母细胞生长在一个贫穷的氮源与NH 4+离子供应,几个氮渗透酶,包括一般的氨基酸通透酶(Gap 1 p)迅速和完全失活。这份报告表明,NH 4+的Gap 1通透酶的失活伴随着其降解。Gap 1 p的失活和降解都需要功能性NPI 1基因产物。对NPI 1基因的分子分析表明,它与RSP 5相同。RSP 5产物是一种泛素-蛋白质连接酶(E3酶),然而其生理功能尚不清楚。其C-末端区域与泛素蛋白连接酶的E6-AP样家族的其他成员非常相似。它的N-末端区域包含一个可能是Ca 2+依赖性磷脂相互作用基序的C-2结构域,随后是最近鉴定的称为WW(P)的结构域的几个拷贝。Npi 1/Rsp 5蛋白在人类和小鼠中都有同源物,后者参与大脑发育。应力诱导的尿嘧啶通透酶(Fur 4p),其中泛素可能参与的过程中的降解,也被发现需要一个功能性的NPI 1/RSP 5产品。NPI 1/RSP 5的染色体缺失表明该基因对细胞活力是必需的。在活的npi 1/rsp 5菌株中,由于在其5'区插入Ty 1元件,NPI 1/RSP 5的表达降低。我们的研究结果表明,Npi 1/Rsp 5泛素蛋白连接酶参与诱导降解的至少两个渗透酶,Gap 1 p和Fur 4p,也可能是其他蛋白质。
When yeast cells growing on a poor nitrogen source are supplied with NH4+ ions, several nitrogen permeases including the general amino acid permease (Gap1p) are rapidly and completely inactivated. This report shows that inactivation by NH4+ of the Gap1 permease is accompanied by its degradation. A functional NPI1 gene product is required for both inactivation and degradation of Gap1p. Molecular analysis of the NPI1 gene showed that it is identical to RSP5. The RSP5 product is a ubiquitin-protein ligase (E3 enzyme) whose physiological function was, however, unknown. Its C-terminal region is very similar to that of other members of the E6-AP-like family of ubiquitin-protein ligases. Its N-terminal region contains a single C-2 domain that may be a Ca2+-dependent phospholipid interaction motif, followed by several copies of a recently identified domain called WW(P). The Npi1/Rsp5 protein has a homologue both in humans and in mice, the latter being involved in brain development. Stress-induced degradation of the uracil permease (Fur4p), a process in which ubiquitin is probably involved, was also found to require a functional NPI1/RSP5 product. Chromosomal deletion of NPI1/RSP5 showed that this gene is essential for cell viability. In the viable npi1/rsp5 strain, expression of NPI1/RSP5 is reduced as a result of insertion of a Ty1 element in its 5' region. Our results show that the Npi1/Rsp5 ubiquitin-protein ligase participates in induced degradation of at least two permeases, Gap1p and Fur4p, and probably also other proteins.