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SCF Fbx4/alphaB-crystallin cyclin D1 ubiquitin ligase: a license to destroy

机译:SCF Fbx4 / alphaB-crystallin细胞周期蛋白D1泛素连接酶:销毁许可证

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Cyclin D1 is an allosteric regulator for cyclin-dependent kinases 4 and 6 (CDK4/6). The cyclin D/CDK4 kinase promotes G1/S transition through the posttranslational modification and the subsequent inactivation of the retinoblastoma (Rb) protein and related family members (p107 and p130). Accumulation of cyclin D1 is tightly regulated through various mechanisms including transcription, protein localization and ubiquitin-dependent proteolysis. While regulators of cyclin D1 gene expression have been under considerable scrutiny, the identity of the protein complex that targets cyclin D1 protein for degradation, the putative E3 ubiquitin ligase, has remained obscure. In a recent report, Lin et al [ 1 ] describe the identification and characterization of a novel SCF, wherein FBX4 and αB-crystallin serve as specificity factors that direct ubiquitination of phosphorylated cyclin D1. As cyclin D1 overexpression in human cancer has been postulated to occur through the loss of degradation machinery, the identification of the SCFFbx4/αB-crystallin ligase will allow new experimental approaches that address mechanisms of cyclin D1 overexpression in human cancer.
机译:细胞周期蛋白D1是细胞周期蛋白依赖性激酶4和6(CDK4 / 6)的变构调节剂。细胞周期蛋白D / CDK4激酶通过翻译后修饰以及随后的成视网膜细胞瘤(Rb)蛋白和相关家族成员的失活来促进G1 / S过渡(p107和p130)。细胞周期蛋白D1的积累受多种机制的严格调控,包括转录,蛋白质定位和泛素依赖性蛋白水解。尽管细胞周期蛋白D1基因表达的调节剂受到了严格的审查,但靶向细胞周期蛋白D1蛋白降解的蛋白质复合物(假定的E3泛素连接酶)的身份仍然不清楚。 Lin等[1]在最近的一份报告中描述了一种新型SCF的鉴定和表征,其中FBX4和αB-crystallin作为指导磷酸化细胞周期蛋白D1泛素化的特异性因子。由于人癌中细胞周期蛋白D1的过表达被认为是由于降解机制的丧失而发生的,因此SCF Fbx4 /αB-晶状体蛋白连接酶的鉴定将为解决细胞周期蛋白D1的过表达机理提供新的实验方法。人类癌症。

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