UBPY: a growth-regulated human ubiquitin isopeptidase
UBPY: a growth-regulated human ubiquitin isopeptidase
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DOI：
10.1093/emboj/17.12.3241
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发表时间：
1998-06-15
期刊：
影响因子：
11.4
通讯作者：
Draetta, GF
中科院分区：
文献类型：
--
作者：
Naviglio, S;Matteucci, C;Draetta, GF
泛素途径涉及控制细胞生长和增殖的蛋白质丰度的调节。我们已经鉴定并鉴定了一种新型人泛素异构肽酶 UBPY，它作为重组蛋白并且在细胞提取物中进行免疫沉淀后能够裂解线性或异肽连接的泛素链。 UBPY 在饥饿的人类成纤维细胞的生长刺激下积累，并且其水平因细胞与细胞接触引起的生长停滞而降低。通过反义质粒显微注射抑制 UBPY 积累，可防止成纤维细胞响应血清刺激而进入 S 期。通过增加或减少 UBPY 的细胞丰度或通过过度表达催化位点突变体，我们检测到蛋白质泛素化总体模式的实质性变化，这与细胞增殖密切相关。我们的结果表明 UBPY 在调节泛素-蛋白酶体途径的整体功能中发挥作用。影响体内特定 UBP 的功能可以为控制哺乳动物细胞增殖提供新的工具。
The ubiquitin pathway has been implicated in the regulation of the abundance of proteins that control cell growth and proliferation. We have identified and characterized a novel human ubiquitin isopeptidase, UBPY, which both as a recombinant protein and upon immunoprecipitation from cell extracts is able to cleave linear or isopeptide-linked ubiquitin chains. UBPY accumulates upon growth stimulation of starved human fibroblasts, and its levels decrease in response to growth arrest induced by cell-cell contact. Inhibition of UBPY accumulation by antisense plasmid microinjection prevents fibroblasts from entering S-phase in response to serum stimulation. By increasing or decreasing the cellular abundance of UBPY or by overexpressing a catalytic site mutant, we detect substantial changes in the total pattern of protein ubiquitination, which correlate stringently with cell proliferation. Our results suggest that UBPY plays a role in regulating the overall function of the ubiquitin-proteasome pathway. Affecting the function of a specific UBP lit vivo could provide novel tools for controlling mammalian cell proliferation.