NPR2, YEAST HOMOLOG OF THE HUMAN TUMOR SUPPRESSOR NPRL2, IS A TARGET OF GRR1

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 Npr 2，一种假定的“氮渗透酶调节剂”和人类肿瘤的同源物 抑制因子NPRL 2被发现与SCF的F盒组分Grr 1（Grr 1）相互作用 （含Grr 1的Skp 1-cullin-F-box蛋白复合物）E3泛素连接酶，按质量计 基于光谱的多维蛋白质鉴定技术。Npr 2有两个PEST 序列，并已在泛素化的蛋白质中鉴定。像其他Grr 1 Npr 2是一种磷蛋白。磷酸化Npr 2在grr 1 δ突变体中积累， 并且Npr 2在具有失活的蛋白酶体的细胞中稳定。磷酸化和不稳定性 依赖于I型酪蛋白激酶（CK 1）Yck 1和Yck 2。Npr 2的过度表达是 对细胞有害，并且在grr 1 δ突变体中是致命的。Npr 2是需要强劲的增长， 含有铵或尿素作为氮源的成分确定的培养基，但不能在 丰富的介质。npr 2Delta突变体也不能有效地完成减数分裂。所有这些 数据表明Npr 2是SCF（Grr 1）E3泛素的磷酸化依赖性靶点 在某些氮源上细胞生长中起作用的连接酶。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Npr2, a putative "nitrogen permease regulator" and homolog of the human tumor suppressor NPRL2, was found to interact with Grr1, the F-box component of the SCF(Grr1) (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 in grr1Delta 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 in grr1Delta 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. npr2Delta mutants also fail to efficiently complete meiosis. Together, these data indicate that Npr2 is a phosphorylation-dependent target of the SCF(Grr1) E3 ubiquitin ligase that plays a role in cell growth on some nitrogen sources.