Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome.
Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome.
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SAP130/SF3B-3与Cullin环泛素连接酶配合物及其通过COP9信号体调节的关联。
DOI：
10.1186/1471-2091-9-1
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发表时间：
2008-01-03
期刊：
影响因子：
--
通讯作者：
Wei, Ning
中科院分区：
文献类型：
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作者：
Menon, Suchithra;Tsuge, Tomohiko;Dohmae, Naoshi;Takio, Koji;Wei, Ning
cullin - ring泛素E3连接酶（CRLs）是通过修饰cullin亚基上的泛素样蛋白Nedd8（也称为Rub1）来调节的。类黄酮化有利于E3复合物的组装；而未修饰的cullins则被CAND1结合，从而阻止底物的募集。Nedd8修饰的水平严重依赖于COP9信号体（CSN），这是一种含有Nedd8异肽酶活性的8个亚基蛋白复合物。我们报道了作为CSN1相互作用蛋白的SAP130 （SF3b-3）的分离。SAP130与DDB1同源，是SF3b RNA剪接复合体和STAGA/TFTC转录复合体的组成部分，但其在这些复合体中的具体功能尚不清楚。我们发现SAP130可以与多种cullin蛋白相互作用。通过结合cullins的n端和C端结构域，与SCFSkp2、伸长蛋白B/C - cul2 - VHL和Cul4-DDB等完全组装的CRL E3复合物形成三级配合物。SAP130在体内优先与类木化cullins结合。然而，CAND1的敲除消除了这种偏好，并增加了SAP130与Cul2的关联。此外，我们提供的证据表明，CSN调节SAP130-Cul2相互作用和sap130相关的多泛素化活性。SAP130是一种cullin结合蛋白，可能参与Nedd8通路。SAP130与多种cullin成员蛋白如Cul1、Cul2和Cul4A的结合受到CAND1和CSN的调节。作为转录和RNA加工复合物的一个已知组分，我们假设SAP130可能将CRL介导的泛素化与基因表达联系起来。
Cullin-RING ubiquitin E3 ligases (CRLs) are regulated by modification of an ubiquitin-like protein, Nedd8 (also known as Rub1) on the cullin subunit. Neddylation is shown to facilitate E3 complex assembly; while un-neddylated cullins are bound by CAND1 that prevents recruitment of the substrates. The level of Nedd8 modification is critically dependent on the COP9 signalosome (CSN), an eight-subunit protein complex containing Nedd8 isopeptidase activity. We report isolation of SAP130 (SF3b-3) as a CSN1 interacting protein. SAP130 is homologous to DDB1, and is a component of SF3b RNA splicing complex and STAGA/TFTC transcription complexes, but its specific function within these complexes is unknown. We show that SAP130 can interact with a variety of cullin proteins. It forms tertiary complexes with fully assembled CRL E3 complexes such as SCFSkp2, Elongin B/C -Cul2- VHL and Cul4-DDB complex by binding to both N-terminal and C-terminal domain of cullins. SAP130 preferentially associates with neddylated cullins in vivo. However knock-down of CAND1 abolished this preference and increased association of SAP130 with Cul2. Furthermore, we provide evidence that CSN regulates SAP130-Cul2 interaction and SAP130-associated polyubiquitinating activity. SAP130 is a cullin binding protein that is likely involved in the Nedd8 pathway. The association of SAP130 with various cullin member proteins such as Cul1, Cul2 and Cul4A is modulated by CAND1 and CSN. As an established component of transcription and RNA processing complexes, we hypothesis that SAP130 may link CRL mediated ubiquitination to gene expression.