KAT8–IRF1 condensation promotes IRF1 K78 acetylation and binding to the CD247 (PD-L1) promoter and further enriches the transcription apparatus to promote transcription of PD-L1 mRNA. Based on the mechanism of KAT8–IRF1 condensate formation, we identified the 2142–R8 blocking peptide, which ...
KAT8–IRF1 condensation promotes IRF1 K78 acetylation and binding to the CD247 (PD-L1) promoter and further enriches the transcription apparatus to promote transcription of PD-L1 mRNA. Based on the mechanism of KAT8–IRF1 condensate formation, we identified the 2142–R8 blocking peptide, which ...
Disruption of KAT8–IRF1 Condensate Formation Reduces PD-L1 Expressiondoi:10.1158/2159-8290.CD-RW2023-042The histone acetyltransferase KAT8 transcriptionally upregulates PD-L1 through cocondensation with IRF1.Cancer Discovery
该研究揭示了KAT8-IRF1凝聚体促进肿瘤细胞PD-L1表达，开发的特异性多肽可阻断凝聚体形成，增强抗肿瘤免疫。为深入揭示IFNγ诱导PD-L1表达的调控机制，研究人员利用全基因组CRISPR-Cas9文库进行筛选，发现乙酰转移酶KAT8可调控PD-L1的表达，这一机制在多种肿瘤细胞系中得到验证。KAT8是细胞内组蛋白H4K16ac主要乙酰...
KAT8已报道可催化非组蛋白底物,研究人员发现KAT8可乙酰化IRF1 K78位点,凝聚体形成可增强催化速率约40倍,IRF1 K78ac可增强与PD-L1启动子结合能力。 根据KAT8-IRF1凝聚体形成的结构基础,研究人员基于IRF1 N端与KAT8的特异性相互作用...