The GNAS Locus: Quintessential Complex Gene Encoding Gsalpha, XLalphas, and other Imprinted Transcripts.
The GNAS Locus: Quintessential Complex Gene Encoding Gsalpha, XLalphas, and other Imprinted Transcripts.
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DOI：
10.2174/138920207783406488
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发表时间：
2007-09
期刊：
影响因子：
2.6
通讯作者：
Bastepe M
中科院分区：
文献类型：
--
作者：
Bastepe M
目前估计的人类基因组中基因的数量比以前预测的要少得多。对于这种差异的解释是，大多数个体基因具有多个转录单位，这些转录单位代表了各种生物学上重要的基因产物。GNAS就是这种复杂基因的一个例子。其产物之一是刺激异三聚体G蛋白（Gsα）的α-亚基，Gsα是一种普遍存在的信号蛋白，对许多不同的细胞反应至关重要。编码gs α-的GNAS外显子的功能丧失和功能获得突变存在于各种人类疾病中，包括Albright遗传性骨营养不良、假性甲状旁腺功能低下、骨纤维性发育不良和一些不同来源的肿瘤。虽然Gsα在大多数组织中的表达是双等位的，但在少数组织中父本Gsα的表达是沉默的，在与GNAS突变相关的表型的发展中起重要作用。其他完全来自父本GNAS等位基因的产物包括XLαs，一种与gsa α部分相同的蛋白质，以及两个非编码RNA分子，a /B转录物和反义转录物。母体GNAS等位基因导致NESP55，一种嗜铬粒蛋白样神经内分泌分泌蛋白。体内动物模型已经证明了每一种独家印迹GNAS产品在正常哺乳动物生理中的重要性。然而，尽管这些产物中的一种或多种也会被大多数自然发生的GNAS突变破坏，但它们在疾病发病机制中的作用仍然未知。为了进一步了解该基因在生理和病理生理中的意义，阐明各GNAS产物的细胞作用和表达调控机制将是重要的。
The currently estimated number of genes in the human genome is much smaller than previously predicted. As an explanation for this disparity, most individual genes have multiple transcriptional units that represent a variety of biologically important gene products. GNAS exemplifies a gene of such complexity. One of its products is the α-subunit of the stimulatory heterotrimeric G protein (Gsα), a ubiquitous signaling protein essential for numerous different cellular responses. Loss-of-function and gain-of-function mutations within Gsα-coding GNAS exons are found in various human disorders, including Albright’s hereditary osteodystrophy, pseudohypoparathyroidism, fibrous dysplasia of bone, and some tumors of different origin. While Gsα expression in most tissues is biallelic, paternal Gsα expression is silenced in a small number of tissues, playing an important role in the development of phenotypes associated with GNAS mutations. Additional products derived exclusively from the paternal GNAS allele include XLαs, a protein partially identical to Gsα, and two non-coding RNA molecules, the A/B transcript and the antisense transcript. The maternal GNAS allele leads to NESP55, a chromogranin-like neuroendocrine secretory protein. In vivo animal models have demonstrated the importance of each of the exclusively imprinted GNAS products in normal mammalian physiology. However, although one or more of these products are also disrupted by most naturally occurring GNAS mutations, their roles in disease pathogenesis remain unknown. To further our understanding of the significance of this gene in physiology and pathophysiology, it will be important to elucidate the cellular roles and the mechanisms regulating the expression of each GNAS product.
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DOI：
10.1073/pnas.83.23.8893
发表时间：
1986-12-01
影响因子：
11.1
作者：
BRAY, P;CARTER, A;NIRENBERG, M
通讯作者：
NIRENBERG, M
影响因子：
15.9
作者：
CHASE, LR;MELSON, GL;AURBACH, GD
通讯作者：
AURBACH, GD
DOI：
10.1073/pnas.0408268102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Chen, M;Gavrilova, O;Weinstein, LS
通讯作者：
Weinstein, LS
DOI：
10.1073/pnas.0308758101
发表时间：
2004-06-01
影响因子：
11.1
作者：
Abramowitz, J;Grenet, D;Birnbaumer, L
通讯作者：
Birnbaumer, L
影响因子：
3.3
作者：
Bauer, R;Ischia, R;Fischer-Colbrie, R
通讯作者：
Fischer-Colbrie, R