HCMV UL36 binds MLKL

Human cytomegalovirus (HCMV) protein pUL36 was found to bind mixed lineage kinase domain-like protein (MLKL) and target MLKL for degradation in HCMV-infected TERT-immortalized primary human fetal foreskin fibroblasts (HFFF-TERTs) (Fletcher-Etherington A et al. 2020). Furthermore, mutation of pUL36 Cys131 abrogated MLKL degradation and restored necroptosis in HFFF-TERTs. The same residue was also required for pUL36-mediated inhibition of apoptosis by preventing proteolytic activation of procaspase-8, suggesting that pUL36 acts as a multifunctional inhibitor of both apoptotic and necroptotic cell death (Fletcher-Etherington A et al. 2020; Skaletskaya A et al. 2001).

人类巨细胞病毒（HCMV）蛋白pUL36被发现可与混合谱系激酶结构域样蛋白（MLKL）结合，并在HCMV感染的人胎儿包皮成纤维细胞（HFFF-TERTs）中靶向MLKL进行降解（Fletcher-Etherington A等，2020年）。此外，pUL36中Cys131位点的突变导致MLKL降解受阻，并恢复HFFF-TERTs中的坏死性凋亡。该位点对于pUL36介导的通过阻止procaspase-8的蛋白水解激活来抑制细胞凋亡亦属必需，这表明pUL36作为一种多功能抑制剂，能够抑制凋亡和坏死性细胞死亡（Fletcher-Etherington A等，2020年；Skaletskaya A等，2001年）。