The cullin7 E3 ubiquitin ligase: a novel player in growth control.

The cullin7 E3 ubiquitin ligase: a novel player in growth control.
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DOI:
10.4161/cc.7.20.6922
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发表时间:
2008-10
期刊:
Cell cycle (Georgetown, Tex.)
影响因子:
--
通讯作者:
Pan ZQ
Pan ZQ
中科院分区:
其他
文献类型:
--
作者:
Sarikas A;Xu X;Field LJ;Pan ZQ

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Cullin 7(CUL 7)是一种分子支架,其组织包含F-box蛋白Fbw 8、Skp 1和ROC 1 RING指蛋白的E3泛素连接酶。CUL 7 E3连接酶的失调与遗传性人类疾病直接相关,因为在常染色体隐性3-M和雅库特身材矮小综合征患者中发现了CUL 7种系突变,其特征在于严重的产前和产后生长迟缓。此外,小鼠中CUL 7的基因消除导致子宫内生长迟缓和围产期死亡,强调了其对生长调节的重要性。最近发现胰岛素受体底物1(胰岛素和胰岛素样生长因子-1信号传导的关键介体)是CUL 7 E3连接酶的蛋白水解靶点,这提供了CUL 7与成熟的生长调节途径之间的分子联系。这一结果,再加上其他研究表明CUL 7和p53肿瘤抑制蛋白,以及猿猴病毒40大T抗原癌蛋白之间的相互作用,进一步暗示CUL 7作为一个新的球员在生长控制和建议的病理机制的见解CUL 7连锁生长迟缓综合征。
Cullin7 (CUL7) is a molecular scaffold that organizes an E3 ubiquitin ligase containing the F-box protein Fbw8, Skp1 and the ROC1 RING finger protein. Dysregulation of the CUL7 E3 Ligase has been directly linked to hereditary human diseases as cul7 germline mutations were found in patients with autosomal-recessive 3-M and Yakuts short stature syndromes, which are characterized by profound pre- and postnatal growth retardation. In addition, genetic ablation of CUL7 in mice resulted in intra-uterine growth retardation and perinatal lethality, underscoring its importance for growth regulation. The recent identification of insulin receptor substrate 1, a critical mediator of insulin and insulin-like growth factor-1 signaling, as the proteolytic target of the CUL7 E3 ligase, provided a molecular link between CUL7 and a well-established growth regulatory pathway. This result, coupled with other studies demonstrating interactions between CUL7 and the p53 tumor suppressor protein, as well as the simian virus 40 large T antigen oncoprotein, further implicated CUL7 as a novel player in growth control and suggested pathomechanistic insights into CUL7-linked growth retardation syndromes.
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