Gli-similar (Glis) Krüppel-like zinc finger proteins: insights into their physiological functions and critical roles in neonatal diabetes and cystic renal disease.
Gli-similar (Glis) Krüppel-like zinc finger proteins: insights into their physiological functions and critical roles in neonatal diabetes and cystic renal disease.
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DOI：
10.14670/hh-25.1481
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发表时间：
2010-11
影响因子：
2
通讯作者：
Jetten AM
中科院分区：
文献类型：
--
作者：
Kang HS;ZeRuth G;Lichti-Kaiser K;Vasanth S;Yin Z;Kim YS;Jetten AM
GLI-类似（Glis）1-3蛋白质构成与Gli家族密切相关的Krüppel样锌指转录因子的亚家族。Glis 1 -3在许多生理过程的调节中起着关键作用，并与多种病理学有关。GLIS 2的突变与肾单位结核（一种常染色体隐性遗传的囊性肾病）有关。Glis 2功能的丧失导致肾萎缩和纤维化，其涉及肾小管上皮细胞的上皮-间质转化（EMT）。人GLIS 3突变与以新生儿糖尿病和先天性甲状腺功能减退症（NDH）为特征的综合征以及一些伴有多囊肾病、青光眼和肝纤维化的患者有关。此外，GLIS 3基因已被确定为1型和2型糖尿病风险的易感基因座。Glis 3在胰腺发育中起关键作用，特别是在β细胞的产生和胰岛素基因表达的调节中。Glis 2和Glis 3蛋白已被证明定位于初级纤毛，初级纤毛是一种与包括囊性肾病在内的多种病理学有关的信号细胞器。这种关联表明Glis 2/3是控制Glis蛋白活性的主要纤毛相关信号通路的一部分。在初级纤毛中激活后，Glis蛋白可以易位到细胞核，在那里它们随后通过与靶基因的启动子调控区中的Glis结合位点相互作用来调节基因转录。在这篇综述中，我们讨论了目前的知识Glis信号通路，它们的生理功能，以及它们在几个人类病理的参与。
GLI-similar (Glis)1–3 proteins constitute a subfamily of the Krüppel-like zinc finger transcription factors that are closely related to the Gli family. Glis1–3 play critical roles in the regulation of a number of physiological processes and have been implicated in several pathologies. Mutations in GLIS2 have been linked to nephronophthisis, an autosomal recessive cystic kidney disease. Loss of Glis2 function leads to renal atrophy and fibrosis that involves epithelial-mesenchymal transition (EMT) of renal tubule epithelial cells. Mutations in human GLIS3 have been implicated in a syndrome characterized by neonatal diabetes and congenital hypothyroidism (NDH) and in some patients accompanied by polycystic kidney disease, glaucoma, and liver fibrosis. In addition, the GLIS3 gene has been identified as a susceptibility locus for the risk of type 1 and 2 diabetes. Glis3 plays a key role in pancreatic development, particularly in the generation of β-cells and in the regulation of insulin gene expression. Glis2 and Glis3 proteins have been demonstrated to localize to the primary cilium, a signaling organelle that has been implicated in several pathologies, including cystic renal diseases. This association suggests that Glis2/3 are part of primary cilium-associated signaling pathways that control the activity of Glis proteins. Upon activation in the primary cilium, Glis proteins may translocate to the nucleus where they subsequently regulate gene transcription by interacting with Glis-binding sites in the promoter regulatory region of target genes. In this review, we discuss the current knowledge of the Glis signaling pathways, their physiological functions, and their involvement in several human pathologies.