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组织转谷氨酰胺酶:从生物胶水到细胞存活信号

Tissue transglutaminase: from biological glue to cell survival cues.

作者信息

Mehta Kapil, Fok Jansina Y, Mangala Lingegowda S

机构信息

Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer, Houston, TX 77030, USA.

出版信息

Front Biosci. 2006 Jan 1;11:173-85. doi: 10.2741/1789.

Abstract

Tissue transglutaminase (TG2, EC 2.3.2.13) is a ubiquitous enzyme that catalyzes Ca2+-dependent post-translational modification of proteins by inserting highly stable (epsilon-[gamma-glutamyl] lysine) isopeptide bonds or by conjugating polyamines at selected peptide-bound glutamine residues. The TG2-catalyzed cross-linked products (generally high molecular mass scaffold of proteins) are of great physiological significance; they are highly stable and resistant to mechanical, chemical and proteolytic degradation. The accumulation of isopeptide bonds can be observed in skin, hair and during blood clotting and wound healing. In addition to transamidation activity, TG2 also exhibits GTPase activity and in response to certain agonist hormones can serve as a signal transducing G protein. Although predominantly a cytosolic protein, TG2 can translocate to the nucleus with the help of importin alpha-3 protein or to the membranes in association with integrins. Moreover, TG2 can also be secreted outside the cell (by yet unknown mechanism) where it crosslinks proteins of the extracellular matrix (ECM) and promotes cell adhesion and spreading. Another important property of TG2 is that it has high binding-affinity for the ECM component protein, fibronectin and thus can promote interaction between cell surface integrin with fibronectin. In this review, we discuss the implications of increased TG2 expression in drug-resistant and metastatic cancer cells and that how TG2 expression can contribute in the development of these phenotypes.

摘要

组织转谷氨酰胺酶(TG2,EC 2.3.2.13)是一种普遍存在的酶,它通过插入高度稳定的(ε-[γ-谷氨酰基]赖氨酸)异肽键或在选定的肽结合谷氨酰胺残基上结合多胺,催化蛋白质的钙离子依赖性翻译后修饰。TG2催化的交联产物(通常是蛋白质的高分子量支架)具有重要的生理意义;它们高度稳定,对机械、化学和蛋白水解降解具有抗性。在皮肤、毛发以及血液凝固和伤口愈合过程中可以观察到异肽键的积累。除了转酰胺基活性外,TG2还表现出GTPase活性,并且在对某些激动剂激素作出反应时可以作为信号转导G蛋白。尽管TG2主要是一种胞质蛋白,但它可以在importinα-3蛋白的帮助下转运到细胞核,或者与整合素结合转运到细胞膜。此外,TG2也可以(通过尚不清楚的机制)分泌到细胞外,在那里它交联细胞外基质(ECM)的蛋白质并促进细胞粘附和扩散。TG2的另一个重要特性是它对ECM成分蛋白纤连蛋白具有高结合亲和力,因此可以促进细胞表面整合素与纤连蛋白之间的相互作用。在这篇综述中,我们讨论了TG2在耐药和转移性癌细胞中表达增加的影响,以及TG2表达如何促进这些表型的发展。

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