State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai, People's Republic of China,
Biotechnol Lett. 2013 Dec;35(12):1983-9. doi: 10.1007/s10529-013-1295-2. Epub 2013 Aug 2.
Endoplasmic reticulum-associated protein degradation (ERAD) removes improperly-folded proteins from the ER membrane into the cytosol where they undergo proteasomal degradation. Valosin-containing protein (VCP)/p97 mediates in the extraction of ERAD substrates from the ER. BRSK2 (also known as SAD-A), a serine/threonine kinase of the AMP-activated protein kinase family affected VCP/p97 activity in ERAD. In addition, BRSK2 interacted with VCP/p97 via three of the four functional domains of VCP/p97. Immunofluorescence demonstrated that BRSK2 and VCP/p97 were co-localized and also that knockdown of endogenous BRSK2 induced increased levels of CD3δ, a substrate in ERAD for VCP/p97. Thus, BRSK2 might affect the activity of VCP/p97 in ERAD.
内质网相关蛋白降解（ERAD）将错误折叠的蛋白质从内质网膜中去除到细胞质中，在那里它们被蛋白酶体降解。含缬氨酸的蛋白（VCP）/ p97 介导 ERAD 底物从内质网中的提取。BRSK2（也称为 SAD-A）是 AMP 激活蛋白激酶家族的丝氨酸/苏氨酸激酶，影响 ERAD 中的 VCP/p97 活性。此外，BRSK2 通过 VCP/p97 的四个功能域中的三个与 VCP/p97 相互作用。免疫荧光显示 BRSK2 和 VCP/p97 共定位，并且内源性 BRSK2 的敲低诱导 VCP/p97 的 ERAD 底物 CD3δ 的水平增加。因此，BRSK2 可能会影响 ERAD 中 VCP/p97 的活性。
