BAP1 as a novel regulator of type I interferon signaling through transcriptional control of key response machinery components
Abstract
Type I interferon (IFN-I) signaling is critical for dual immunity, defending against microbial infections and augmenting anti-tumor immune responses. Research in the past few decades have identified the key machinery components and over 300 interferon-stimulated genes (ISGs) that comprise the IFN-I signaling network. While cascade amplification mechanisms ensure robust pathway activation, appropriate expression of signaling components is essential for maintaining pathway sensitivity, enabling efficient signal amplification, and providing adequate host responses. Here, we identified BRCA1-associated protein-1 (BAP1) as a positive regulator of the IFN-I signaling pathway through a genome-wide CRISPR/Cas9 screen in murine macrophage Raw264.7 cells stimulated with cGAMP. We confirmed both the enzymatic activity and nuclear localization of BAP1 were essential for this regulation. Our findings reveal that BAP1 regulates a broad transcriptional program essential for IFN-I responses, including IFNAR1 and IFNAR2. BAP1 deficient cells failed to mount an effective IFN-I response, showing markedly reduced ISGs and resulting in uncontrolled viral replication. These findings together highlight an essential role of BAP1 in controlling IFN-I signaling and antiviral responses.
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BibTeX
@article{mortazavi2026bap1,
title = {{BAP1 as a novel regulator of type I interferon signaling through transcriptional control of key response machinery components}},
author = {Yasaman Mortazavi and Hanyue Zhang and Robert Herrera and Ryan Cook and Bo Zhong and Dandan Lin and Yue Zhao},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1831576},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1831576},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - BAP1 as a novel regulator of type I interferon signaling through transcriptional control of key response machinery components
AU - Yasaman Mortazavi
AU - Hanyue Zhang
AU - Robert Herrera
AU - Ryan Cook
AU - Bo Zhong
AU - Dandan Lin
AU - Yue Zhao
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1831576
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1831576
AB - Type I interferon (IFN-I) signaling is critical for dual immunity, defending against microbial infections and augmenting anti-tumor immune responses. Research in the past few decades have identified the key machinery components and over 300 interferon-stimulated genes (ISGs) that comprise the IFN-I signaling network. While cascade amplification mechanisms ensure robust pathway activation, appropriate expression of signaling components is essential for maintaining pathway sensitivity, enabling efficient signal amplification, and providing adequate host responses. Here, we identified BRCA1-associated protein-1 (BAP1) as a positive regulator of the IFN-I signaling pathway through a genome-wide CRISPR/Cas9 screen in murine macrophage Raw264.7 cells stimulated with cGAMP. We confirmed both the enzymatic activity and nuclear localization of BAP1 were essential for this regulation. Our findings reveal that BAP1 regulates a broad transcriptional program essential for IFN-I responses, including IFNAR1 and IFNAR2. BAP1 deficient cells failed to mount an effective IFN-I response, showing markedly reduced ISGs and resulting in uncontrolled viral replication. These findings together highlight an essential role of BAP1 in controlling IFN-I signaling and antiviral responses.
SN - 1664-3224
ER -