Novel proteases with deubiquitylation activity: examination of function in T lymphocytes
具有去泛素化活性的新型蛋白酶:T 淋巴细胞功能检查
基本信息
- 批准号:G0501068/1
- 负责人:
- 金额:$ 40.98万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2006
- 资助国家:英国
- 起止时间:2006 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Work over the last 25 years has established the importance of regulating protein ubiquitylation in a wide range of cellular functions including cell cycle control, transcriptional regulation, and cell signaling. These processes are disturbed in many human diseases such as cancer, neurodegeneration and immunological disorders. So far, most analyses have focused on mechanisms controlling ubiquitin ligation. However, the recognition of extensive classes of deubiquitylating enzymes (DUBs) strongly suggests a regulatory (as opposed to purely recycling) role for DUBs. Thus it is anticipated that the planned analysis of one class of these enzymes would shed light on important and medically relevant aspects of cellular physiology. A novel class of these enzymes containing an ovarian tumor domain (OTU), which encodes for a putative ubiquitin-specific cysteine protease, has been recently identified. This domain is conserved throughout evolution. Obubain 1 (OTUB1), a member of this protein family, does not contribute to the deubiquitylation of the bulk of cytosolic proteins. Preliminary evidence suggests that OTUB1 plays a specific role in the regulation of antigen responsiveness of T lymphocytes. Insights into this process could have important implications for our understanding of immune-modulation, and may identify OTU containing proteins as novel therapeutic targets.
过去25年的工作已经确立了调节蛋白质泛素化在广泛的细胞功能中的重要性,包括细胞周期控制、转录调节和细胞信号传导。这些过程在许多人类疾病中受到干扰,如癌症、神经变性和免疫紊乱。到目前为止,大多数分析都集中在控制泛素连接的机制上。然而,广泛种类的去泛素化酶(DUBs)的识别强烈表明DUBs具有调节(而不是纯粹的再循环)作用。因此,预计对其中一类酶的计划分析将阐明细胞生理学的重要和医学相关方面。最近发现了一类含有卵巢肿瘤结构域(OTU)的新型酶,该结构域编码一种假定的泛素特异性半胱氨酸蛋白酶。这个区域在整个进化过程中是保守的。奥巴马蛋白1 (OTUB1)是该蛋白家族的一员,不参与大部分细胞质蛋白的去泛素化。初步证据表明,OTUB1在T淋巴细胞的抗原反应性调节中发挥特异性作用。深入了解这一过程可能对我们理解免疫调节具有重要意义,并可能确定含有OTU的蛋白质作为新的治疗靶点。
项目成果
期刊论文数量(0)
专著数量(0)
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Benedikt Kessler其他文献
P113 - Investigating the redox-effector functions of BH4: Insights from <em>in vitro</em> studies of NO–redox balance
- DOI:
10.1016/j.niox.2014.09.061 - 发表时间:
2014-11-15 - 期刊:
- 影响因子:
- 作者:
Jade Bailey;Joanna McGouran;Eileen McNeill;Benedikt Kessler;Keith Channon;Mark Crabtree - 通讯作者:
Mark Crabtree
2143 QUANTITATIVE PROTEOMICS IDENTIFIES CERULOPLASMIN AS A POTENTIAL PROMOTER OF UROLITHIASIS
- DOI:
10.1016/j.juro.2011.02.2354 - 发表时间:
2011-04-01 - 期刊:
- 影响因子:
- 作者:
Cynthia Wright;Sarah Howles;David Trudgian;Benedikt Kessler;John Reynard;Jeremy Noble;Freddie Hamdy;Benjamin Turney - 通讯作者:
Benjamin Turney
Benedikt Kessler的其他文献
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{{ truncateString('Benedikt Kessler', 18)}}的其他基金
Substrate Peptidomimetic Inhibitors (SPIs) of the COP9 signalosome
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EP/N034295/1 - 财政年份:2016
- 资助金额:
$ 40.98万 - 项目类别:
Research Grant
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