The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage
The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage
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DOI：
10.1016/s0092-8674(03)00316-7
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发表时间：
2003-05-02
期刊：
影响因子：
64.5
通讯作者：
Nakatani, Y
中科院分区：
文献类型：
--
作者：
Groisman, R;Polanowska, J;Nakatani, Y
核苷酸切除修复（NER）是一种主要的细胞防御来自太阳的紫外线的致癌作用。NER蛋白如DDB和CSA的突变失活导致遗传性疾病，如着色性干皮病（XP）和Cockayne综合征（CS）。在这里，我们表明，DDB2和CSA通过与DDB1的相互作用被整合到几乎相同的复合物中。两种复合物均含有cullin 4A和Roc 1，并显示泛素连接酶活性。它们还含有COP9信号体（CSN），一种已知的基于cullin的泛素连接酶的调节剂。引人注目的是，CSN差异调节泛素连接酶活性的DDB2和CSA复合物响应于UV照射。用RNA干扰敲低CSN导致NER缺陷。这些结果表明，DDB2和CSA复合物的不同UV响应参与NER的不同机制。
Nucleotide excision repair (NER) is a major cellular defense against the carcinogenic effects of ultraviolet light from the sun. Mutational inactivation of NER proteins, like DDB and CSA, leads to hereditary diseases such as xeroderma pigmentosum (XP) and Cockayne syndrome (CS). Here, we show that DDB2 and CSA are each integrated into nearly identical complexes via interaction with DDB1. Both complexes contain cullin 4A and Roc1 and display ubiquitin ligase activity. They also contain the COP9 signalosome (CSN), a known regulator of cullin-based ubiquitin ligases. Strikingly, CSN differentially regulates ubiquitin ligase activity of the DDB2 and CSA complexes in response to UV irradiation. Knockdown of CSN with RNA interference leads to defects in NER. These results suggest that the distinct UV response of the DDB2 and CSA complexes is involved in diverse mechanisms of NER.