Sen Nirmalya, Gui Bin, Kumar Rakesh
Department of Biochemistry and Molecular Medicine, George Washington University, Washington, DC, 20037, USA.
Cancer Metastasis Rev. 2014 Dec;33(4):869-77. doi: 10.1007/s10555-014-9514-4.
Although the functional significance of the metastasic tumor antigen (MTA) family of chromatin remodeling proteins in the pathobiology of cancer is fairly well recognized, the physiological role of MTA proteins continues to be an understudied research area and is just beginning to be recognized. Similar to cancer cells, MTA1 also modulates the expression of target genes in normal cells either by acting as a corepressor or coactivator. In addition, physiological functions of MTA proteins are likely to be influenced by its differential expression, subcellular localization, and regulation by upstream modulators and extracellular signals. This review summarizes our current understanding of the physiological functions of the MTA proteins in model systems. In particular, we highlight recent advances of the role MTA proteins play in the brain, eye, circadian rhythm, mammary gland biology, spermatogenesis, liver, immunomodulation and inflammation, cellular radio-sensitivity, and hematopoiesis and differentiation. Based on the growth of knowledge regarding the exciting new facets of the MTA family of proteins in biology and medicine, we speculate that the next burst of findings in this field may reveal further molecular regulatory insights of non-redundant functions of MTA coregulators in the normal physiology as well as in pathological conditions outside cancer.
尽管染色质重塑蛋白的转移瘤抗原(MTA)家族在癌症病理生物学中的功能意义已得到相当充分的认识,但MTA蛋白的生理作用仍是一个研究不足的领域,且才刚刚开始被认识。与癌细胞类似,MTA1也通过作为共抑制因子或共激活因子来调节正常细胞中靶基因的表达。此外,MTA蛋白的生理功能可能会受到其差异表达、亚细胞定位以及上游调节因子和细胞外信号调控的影响。本综述总结了我们目前对模型系统中MTA蛋白生理功能的理解。特别是,我们重点介绍了MTA蛋白在大脑、眼睛、昼夜节律、乳腺生物学、精子发生、肝脏、免疫调节和炎症、细胞辐射敏感性以及造血和分化中所起作用的最新进展。基于对MTA蛋白家族在生物学和医学中令人兴奋的新方面的认识不断增长,我们推测该领域的下一波发现可能会揭示MTA共调节因子在正常生理学以及癌症以外的病理条件下非冗余功能的进一步分子调控见解。