Brayman Melissa, Thathiah Amantha, Carson Daniel D
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Reprod Biol Endocrinol. 2004 Jan 7;2:4. doi: 10.1186/1477-7827-2-4.
MUC1 is a large, transmembrane mucin glycoprotein expressed at the apical surface of a variety of reproductive tract epithelia. Functions attributed to MUC1 include those generally associated with mucins such as lubrication and hydration of cell surfaces as well as protection from microorganisms and degradative enzymes. In addition, MUC1 is an effective inhibitor of both cell-cell and cell-extracellular matrix interactions in both normal and malignant contexts. Moreover, a series of recent studies has shown that the highly conserved cytoplasmic tail of MUC1 interacts specifically with a series of important signal transducing molecules including beta-catenin, Grb2 and erbB family members. MUC1 expression in normal epithelia can be quite dynamic, varying in response to steroid hormone or cytokine influences. Following malignant transformation, MUC1 often becomes highly overexpressed, loses its apical restriction, and displays aberrant glycosylation and altered mRNA splice variants. Regulation of MUC1 expression can occur at the transcriptional level. In addition, post-translational regulation of cell surface expression occurs via the activity of cell surface proteases or "sheddases" that release soluble forms of the large ectodomains. This review will briefly summarize studies of MUC1 expression and function in reproductive tissues with particular emphasis on the uterus. In addition, current knowledge of the mechanisms of MUC1 gene regulation, metabolic processing and potential signal transducing functions will be presented.
MUC1是一种大型跨膜粘蛋白糖蛋白，表达于多种生殖道上皮的顶端表面。MUC1的功能包括那些通常与粘蛋白相关的功能，如细胞表面的润滑和水合作用，以及抵御微生物和降解酶。此外，在正常和恶性环境中，MUC1都是细胞间和细胞与细胞外基质相互作用的有效抑制剂。而且，一系列近期研究表明，MUC1高度保守的细胞质尾巴与一系列重要的信号转导分子特异性相互作用，包括β-连环蛋白、Grb2和erbB家族成员。MUC1在正常上皮中的表达可能相当动态，会因类固醇激素或细胞因子的影响而变化。恶性转化后，MUC1常常高度过表达，失去其顶端限制，并表现出异常糖基化和改变的mRNA剪接变体。MUC1表达的调控可发生在转录水平。此外，细胞表面表达的翻译后调控通过细胞表面蛋白酶或“脱落酶”的活性发生，这些酶释放出大的胞外域的可溶性形式。本综述将简要总结MUC1在生殖组织中的表达和功能研究，特别强调子宫。此外，还将介绍目前关于MUC1基因调控、代谢加工和潜在信号转导功能机制的知识。
