Authors
Han Guan, Likai Mao, Fang Fang, Tiange Wu, Yifei Cheng, Zonghao You, Hao Lin, Ruixin Zhang, Junyong Zhuang, Gao-Jun Teng, Chuanjun Shu, Shenghong Ju, Ming Chen, Wenchao Li, Bin Xu
Published in
Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 30. Pages e2603231123. Jul 28, 2026. Epub Jul 21, 2026.
Abstract
Loss of major histocompatibility complex (MHC)-I is a hallmark of prostate cancer (PCa) immune evasion and immunotherapy failure. Here, we identify ZNF263 as a transcriptional repressor that silences MHC-I by recruiting nucleosome-remodeling and deacetylase (NuRD) to the STAT1 promoter, reducing STAT1 and MHC-I expression. Hypoxia enhances this repression through two ZNF263 modifications: phosphorylation-driven phase separation that strengthens NuRD interaction and O-GlcNAcylation at S662 that aids STAT1 promoter binding. O-GlcNAcylation also promotes interaction with protein kinase, DNA‑activated catalytic subunit (PRKDC), amplifying phosphorylation. Interferon‑gamma (IFN‑γ)‑induced MHC-I induction is augmented upon ZNF263 loss. In silico docking identified Viroptic as a Krüppel‑associated box (KRAB) pocket binder disrupting ZNF263-NuRD, derepressing STAT1, and potentiating IFN-γ antitumor immunity in vivo. High ZNF263 correlates with low MHC-I, scarce CD8+ T cells, and poor survival, providing rationale for targeting ZNF263 in PCa immunotherapy.
PMID:
42479843
Bibliographic data and abstract were imported from PubMed on 22 Jul 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 32
- Comments 0