GSK3B介导的PD-L1(CD274)泛素化降解通路
中文名称
通路描述
PD-L1（CD274）的翻译后修饰（PTMs）在正常生理中调节免疫耐受发挥重要作用。该机制被癌细胞劫持以实现免疫逃逸。PD-L1蛋白水平受多种机制（如磷酸化、糖基化、泛素化等）严格调控。GSK3B是一种丝氨酸 - 苏氨酸激酶，受EGFR、WNT等生长因子信号通路调控。GSK3B处于持续激活状态，上游通路的磷酸化使其失活。GSK3B调控PD-L1的蛋白稳定性和糖基化。GSK3B对PD-L1在T180和S184位点的磷酸化诱导其泛素化降解并抑制其糖基化。GSK3B诱导的磷酸化促进PD-L1与β-TrCP（BTRC）结合，后者是SCF E3泛素化酶复合物的底物识别亚基，促进PD-L1泛素化并引导其进入泛素化降解途径（Li et al, 2016, Schulz et al., 2019）。此外，MET磷酸化GSK3B在酪氨酸56位点，导致GSK3B激活并促进PD-L1降解（Li et al, 2019）。
英文描述
Defective visual phototransduction due to STRA6 loss of function Defects in STRA6 cause microphthalmia syndromic type 9 (MCOPS9, Matthew-Wood syndrome or Spear syndrome; MIM:601186) (Chassaing et al. 2009). Mutiple systems are affected by this fatal syndrome including occular and cardiac abnormalities. Microphthalmia (also called microphthalmos, nanophthalmia or nanophthalmos) is a developmental disorder of the eye that literally means small eye and in most cases results in blindness.
所含基因
2 个基因