Open AccessNpr2, Yeast Homolog of the Human Tumor Suppressor NPRL2 , Is a Target of Grr1 Required for Adaptation to Growth on Diverse Nitrogen Sources
Author(s) -
Nathalie Spielewoy,
Marisela Guaderrama,
James A. Wohlschlegel,
Mabelle Ashe,
John R. Yates,
Curt Wittenberg
Publication year - 2010
Publication title -
eukaryotic cell
Language(s) - English
Resource type - Journals
eISSN - 1535-9778
pISSN - 1535-9786
DOI - 10.1128/ec.00192-09
Subject(s) - biology , phosphorylation , cullin , biochemistry , ubiquitin ligase , mutant , asparagine , microbiology and biotechnology , ubiquitin , amino acid , gene
Npr2, a putative “nitrogen permease regulator” and homolog of the human tumor suppressorNPRL2 , was found to interact with Grr1, the F-box component of the SCFGrr1 (Skp1–cullin–F-box protein complex containing Grr1) E3 ubiquitin ligase, by mass spectrometry-based multidimensional protein identification technology. Npr2 has two PEST sequences and has been previously identified among ubiquitinated proteins. Like other Grr1 targets, Npr2 is a phosphoprotein. Phosphorylated Npr2 accumulates ingrr1 Δ mutants, and Npr2 is stabilized in cells with inactivated proteasomes. Phosphorylation and instability depend upon the type I casein kinases (CK1) Yck1 and Yck2. Overexpression of Npr2 is detrimental to cells and is lethal ingrr1 Δ mutants. Npr2 is required for robust growth in defined medium containing ammonium or urea as a nitrogen source but not for growth on rich medium.npr2 Δ mutants also fail to efficiently complete meiosis. Together, these data indicate that Npr2 is a phosphorylation-dependent target of the SCFGrr1 E3 ubiquitin ligase that plays a role in cell growth on some nitrogen sources.