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本文引用的文献

1
A genome-wide screen for regulators of TORC1 in response to amino acid starvation reveals a conserved Npr2/3 complex.一项针对TORC1在应对氨基酸饥饿时的调节因子进行的全基因组筛选揭示了一种保守的Npr2/3复合体。
PLoS Genet. 2009 Jun;5(6):e1000515. doi: 10.1371/journal.pgen.1000515. Epub 2009 Jun 12.
2
A proteomic screen reveals SCFGrr1 targets that regulate the glycolytic-gluconeogenic switch.蛋白质组学筛选揭示了调节糖酵解-糖异生转换的SCFGrr1靶点。
Nat Cell Biol. 2007 Oct;9(10):1184-91. doi: 10.1038/ncb1639. Epub 2007 Sep 9.
3
The yeast ammonium transport protein Mep2 and its positive regulator, the Npr1 kinase, play an important role in normal and pseudohyphal growth on various nitrogen media through retrieval of excreted ammonium.酵母铵转运蛋白Mep2及其正向调节因子Npr1激酶,通过回收分泌的铵,在各种氮源培养基上的正常生长和假菌丝生长中发挥重要作用。
Mol Microbiol. 2007 Apr;64(2):534-46. doi: 10.1111/j.1365-2958.2007.05681.x.
4
Proteasome inhibition in wild-type yeast Saccharomyces cerevisiae cells.野生型酿酒酵母细胞中的蛋白酶体抑制作用。
Biotechniques. 2007 Feb;42(2):158, 160, 162. doi: 10.2144/000112389.
5
The 3p21.3 tumor suppressor NPRL2 plays an important role in cisplatin-induced resistance in human non-small-cell lung cancer cells.位于3p21.3区域的肿瘤抑制基因NPRL2在顺铂诱导的人非小细胞肺癌细胞耐药中发挥重要作用。
Cancer Res. 2006 Oct 1;66(19):9682-90. doi: 10.1158/0008-5472.CAN-06-1483.
6
Constraining G1-specific transcription to late G1 phase: the MBF-associated corepressor Nrm1 acts via negative feedback.将G1期特异性转录限制在G1晚期:与MBF相关的共抑制因子Nrm1通过负反馈发挥作用。
Mol Cell. 2006 Aug;23(4):483-96. doi: 10.1016/j.molcel.2006.06.025.
7
Regulation of transcription factor latency by receptor-activated proteolysis.通过受体激活的蛋白水解作用对转录因子潜伏状态的调控。
Genes Dev. 2006 Jun 15;20(12):1563-8. doi: 10.1101/gad.374206.
8
Platinum-intercalator conjugates: from DNA-targeted cisplatin derivatives to adenine binding complexes as potential modulators of gene regulation.铂嵌入剂共轭物:从靶向DNA的顺铂衍生物到作为基因调控潜在调节剂的腺嘌呤结合复合物。
Curr Top Med Chem. 2004;4(15):1537-49. doi: 10.2174/1568026043387313.
9
Amino acid signaling in yeast: casein kinase I and the Ssy5 endoprotease are key determinants of endoproteolytic activation of the membrane-bound Stp1 transcription factor.酵母中的氨基酸信号传导:酪蛋白激酶I和Ssy5内蛋白酶是膜结合型Stp1转录因子内蛋白水解激活的关键决定因素。
Mol Cell Biol. 2004 Nov;24(22):9771-85. doi: 10.1128/MCB.24.22.9771-9785.2004.
10
Regulation and recognition of SCFGrr1 targets in the glucose and amino acid signaling pathways.葡萄糖和氨基酸信号通路中SCFGrr1靶点的调控与识别
Mol Cell Biol. 2004 Oct;24(20):8994-9005. doi: 10.1128/MCB.24.20.8994-9005.2004.

Npr2是人类肿瘤抑制因子NPRL2的酵母同源物,是适应多种氮源生长所需的Grr1的靶标。

Npr2, yeast homolog of the human tumor suppressor NPRL2, is a target of Grr1 required for adaptation to growth on diverse nitrogen sources.

作者信息

Spielewoy Nathalie, Guaderrama Marisela, Wohlschlegel James A, Ashe Mabelle, Yates John R, Wittenberg Curt

机构信息

Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

出版信息

Eukaryot Cell. 2010 Apr;9(4):592-601. doi: 10.1128/EC.00192-09. Epub 2010 Feb 12.

DOI:10.1128/EC.00192-09
PMID:20154027
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2863403/
Abstract

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.

摘要

Npr2是一种假定的“氮通透酶调节因子”,也是人类肿瘤抑制因子NPRL2的同源物。通过基于质谱的多维蛋白质鉴定技术发现,它能与SCF(Grr1)(包含Grr1的Skp1-泛素连接酶E3泛素连接酶的F-box成分)的F-box成分Grr1相互作用。Npr2有两个PEST序列,并且之前已在泛素化蛋白中被鉴定出来。与其他Grr1靶点一样,Npr2是一种磷蛋白。磷酸化的Npr2在grr1Delta突变体中积累,并且在蛋白酶体失活的细胞中Npr2会稳定下来。磷酸化和不稳定性取决于I型酪蛋白激酶(CK1)Yck1和Yck2。Npr2的过表达对细胞有害,并且在grr1Delta突变体中是致死的。在以铵或尿素作为氮源的限定培养基中,Npr2是强劲生长所必需的,但在丰富培养基上生长则不需要。npr2Delta突变体也无法有效地完成减数分裂。总之,这些数据表明Npr2是SCF(Grr1) E3泛素连接酶的磷酸化依赖性靶点,在某些氮源上的细胞生长中发挥作用。