Sorting Nexin 6 Interacts with Cullin3 and Regulates Programmed Death ‐ligand 1 Expression

AbstractProgrammed death-ligand 1 (PD-L1) is critical for the ability of cancer cells to evade attacks by the host immune system. However, the molecular mechanisms controlling PD-L1 expression have not been fully understood. Here, we demonstrate that sorting nexin 6 (SNX6) is a novel regulator of PD-L1 expression. Knockdown of SNX6 in cancer cells significantly decreases PD-L1 protein levels. In contrast, loss of SNX6 does not reduce PD-L1 mRNA levels. Instead, SNX6 interacts with Cullin3, an E3 ubiquitin ligase responsible for PD-L1 ubiquitination and subsequent degradation. By binding with Cullin3, SNX6 decreases the interaction between the adaptor protein speckle-type POZ protein (SPOP) and Cullin3, which in turn downregulates Cullin3-mediated PD-L1 ubiquitination. This research reveals a novel molecular nexus in modulating PD-L1.

Source: FEBS Letters - September 13, 2021 Category: Biochemistry Authors: Chinmoy Ghosh, Yanli Xing, Suhua Li, Rosalie G. Hoyle, Ming Sun, Jiong Li, Yue Sun Tags: RESEARCH ARTICLE Source Type: research