Coscoy Laurent, Ganem Don
Department of Microbiology, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143-0414, USA.
Trends Cell Biol. 2003 Jan;13(1):7-12. doi: 10.1016/s0962-8924(02)00005-3.
PHD domains constitute a widely distributed subfamily of zinc fingers whose biochemical functions have been unclear until now. Recently, several PHD-containing viral proteins have been identified that promote immune evasion by downregulating proteins that govern immune recognition. Studies show that these viral regulators lead to ubiquitination of their targets by functioning as E3 ubiquitin ligases -- an activity that requires the PHD motif. These are the first examples linking the PHD domain to E3 activity, but the recent discovery of PHD-dependent E3 activity in the cellular kinase MEKK1 and the close structural relation of PHD domains to RING fingers hint that many other PHD proteins might share this activity.
PHD结构域构成了锌指蛋白中广泛分布的一个亚家族，其生化功能至今仍不清楚。最近，已鉴定出几种含PHD的病毒蛋白，它们通过下调调控免疫识别的蛋白来促进免疫逃逸。研究研究表明这些病毒调节因子通过作为E3泛素连接酶发挥作用，导致其靶标发生泛素化——这一活性需要PHD基序。这些是将PHD结构域与E3活性联系起来的首个实例，但最近在细胞激酶MEKK1中发现了依赖PHD的E3活性，且PHD结构域与指环结构域在结构上密切相关，这暗示许多其他含PHD的蛋白可能也具有这种活性。
