Laboratory for Molecular Cancer Biology, VIB-KULeuven, O&N I Herestraat 49, Leuven, Belgium.
Nat Rev Cancer. 2012 Jun 7;12(7):455-64. doi: 10.1038/nrc3271.
COP1 is an E3 ubiquitin ligase that is involved in the ubiquitylation of various protein substrates to trigger their proteasomal degradation. Although originally identified in a light signalling pathway in plants, biochemical studies have identified putative targets of mammalian COP1 with relevant roles in tumorigenesis, including the oncoproteins JUN and ETV family members, as well as the p53 tumour suppressor. Recent genetic studies have shown that COP1 deficiency leads to spontaneous tumour formation in mice, and have identified mutations in COP1 and its substrates in various human cancers. These findings add to our growing appreciation of the roles for E3 ligases in cancer.
COP1 是一种 E3 泛素连接酶，参与多种蛋白质底物的泛素化，从而触发其蛋白酶体降解。尽管最初在植物的光信号通路中被鉴定出来，但生化研究已经鉴定出哺乳动物 COP1 的假定靶标，这些靶标在肿瘤发生中具有相关作用，包括癌蛋白 JUN 和 ETV 家族成员以及抑癌基因 p53。最近的遗传研究表明，COP1 缺失会导致小鼠自发性肿瘤形成，并在各种人类癌症中鉴定出 COP1 及其底物的突变。这些发现增加了我们对 E3 连接酶在癌症中的作用的认识。
