Cullin 4A associates with the UV-damaged DNA-binding protein DDB
Cullin 4A associates with the UV-damaged DNA-binding protein DDB
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DOI：
10.1074/jbc.274.50.35309
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发表时间：
1999-12-10
影响因子：
4.8
通讯作者：
Raychaudhuri, P
中科院分区：
文献类型：
--
作者：
Shiyanov, P;Nag, A;Raychaudhuri, P
受损的DNA结合蛋白（DDB）被认为参与DNA修复，并且它与修复缺陷性疾病着色性干皮病有关。DDB还表现出转录活性。DDE与E2 F1的激活结构域结合并刺激E2 F1激活的转录。在这里，我们提供的证据表明，DDB或DDB相关蛋白的目标cullin 4A（CUL-4A）。CUL-4A是cullin蛋白家族的成员，其被认为是泛素-蛋白质异肽连接酶（E3型）。CUL-4A基因在乳腺癌中被扩增和上调。在这项研究中，我们确定CUL-4A作为DDB相关蛋白之一。CUL-4A与DDE共免疫沉淀，但不与DDB的天然突变体共免疫沉淀。此外，HeLa细胞核提取物中的CUL-4A与DDB共纯化，表明它们是同一复合物的一部分。该观察提供了CUL-4A如何通过与DDB的相互作用在乳腺癌的发展中发挥作用的见解。
The damaged DNA-binding protein (DDB) is believed to be involved in DNA repair, and it has been linked to the repair deficiency disease xeroderma pigmentosum. DDB also exhibits transcriptional activities. DDE binds to the activation domain of E2F1 and stimulates E2F1-activated transcription. Here we provide evidence that DDB or DDB-associated proteins are targets of cullin 4A (CUL-4A). CUL-4A is a member of the cullin family of proteins, which are believed to be ubiquitin-protein isopeptide ligases (type E3). The CUL-4A gene has been shown to be amplified and up-regulated in breast carcinomas. In this study, we identify CUL-4A as one of the DDB-associated proteins. CUL-4A co-immunoprecipitates with DDE, but not with a naturally occurring mutant of DDB, Moreover, CUL-4A in HeLa nuclear extracts co-purifies with DDB, suggesting they are parts of the same complex. The observation provides insights how CUL-4A, through an interaction with DDB, might be playing a role in the development of breast carcinomas.