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NPI1 , an essential yeast gene involved in induced degradation of Gap1 and Fur4 permeases, encodes the Rsp5 ubiquitin—protein ligase
Author(s) -
Hein Claudine,
Springael JeanYves,
Volland Christiane,
HaguenauerTsapis Rosine,
André Bruno
Publication year - 1995
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.1995.mmi_18010077.x
Subject(s) - permease , ubiquitin ligase , biology , biochemistry , ubiquitin , dna ligase , gene product , protein degradation , gene , mutant , gene expression
When yeast cells growing on a poor nitrogen source are supplied with NH 4 + ions, several nitrogen permeases including the general amino acid permease (Gap1p) are rapidly and completely inactivated. This report shows that inactivation by NH 4 + 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 Ca 2+ ‐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 np1/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.