Human tissue kallikreins: A road under construction
Human tissue kallikreins: A road under construction
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DOI：
10.1016/j.cca.2007.02.023
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发表时间：
2007-05-01
影响因子：
5
通讯作者：
Diamandis, Eleftherios P.
中科院分区：
文献类型：
--
作者：
Emami, Nashmil;Diamandis, Eleftherios P.
背景：人组织激肽释放酶基因家族位于染色体19q13.4，是人类基因组中最大的相邻蛋白水解酶家族。该基因座编码该家族的所有15个成员，其中13个已被报道为几种癌症和其他非肿瘤性疾病的潜在生物标记物。激肽释放酶在多种组织中表达，参与多种生理功能，包括皮肤脱皮、精液液化、神经可塑性和调节血压。激肽释放酶的功能受到转录、翻译和翻译后不同水平的调控。激肽释放酶的蛋白分解活性被认为是级联介导的，并可能与其他蛋白水解酶发生串扰。这些级联反应通过一系列反馈环、抑制物、(自动)降解和内部切割受到高度调控。激肽释放酶失控的蛋白分解活性与许多肿瘤和非肿瘤的病理状态有关。结论：随着我们对其调节和功能机制的了解不断扩大，激肽释放酶有望成为设计新的治疗药物的新靶点。(C)2007 Elsevier B.V.保留所有权利。
Background: The human tissue kallikrein gene family, located at chromosome 19q13.4, is the largest contiguous family of proteases in the human genome. The locus encodes all 15 members of the family, 13 of which have been reported as potential biomarkers for several carcinomas and other non-neoplastic diseases. Kallikreins are expressed by a wide range of tissues and implicated in a number of physiological functions, including skin desquamation, semen liquefaction, neural plasticity and the regulation of blood pressure. Kallikrein function is regulated at various levels, including transcription, translation and post-translation. The proteolytic activity of kallikreins is believed to be cascade mediated and may crosstalk with other proteases. These cascades are highly regulated through a series of feedback loops, inhibitors, (auto) degradation and internal cleavage. Uncontrolled proteolytic activity of kallikreins is implicated in a large number of neoplastic and non-neoplastic pathological conditions.Conclusions: As our understanding of their regulatory and functional mechanisms continues to expand, kallikreins are expected to become novel targets for the design of new therapeutics. (c) 2007 Elsevier B.V. All rights reserved.