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Updated: May 7, 2025

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Nuclear transmembrane protein 199 promotes immune escapes by up-regulating programmed death ligand 1

Wulin You1,2,3, Hue Luu3, Meili Li4

  • 1Department of Orthopedics, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, Jiangsu Province, China.

Iscience
|January 6, 2025
PubMed

Insights

Transmembrane protein 199 (TMEM199) localizes to the nucleus and regulates PD-L1 expression by binding to key transcription factors. This finding reveals TMEM199's role in cancer immune regulation.

Area of Science:

  • Molecular biology
  • Cancer research
  • Immunology

Background:

  • The role of transmembrane protein 199 (TMEM199) in cancer remains largely unexplored.
  • Understanding TMEM199's function is crucial for cancer development insights.

Purpose of the Study:

  • To investigate the nuclear localization of TMEM199.
  • To elucidate TMEM199's function in regulating immune checkpoints, specifically PD-L1.
  • To analyze TMEM199's impact on the tumor immune microenvironment.

Main Methods:

  • Utilized Cut&Tag assay to map nuclear-located TMEM199 binding sites.
  • Performed in vitro and in vivo experiments to assess TMEM199's influence on PD-L1.
  • Analyzed interactions between TMEM199 and transcription factors regulating PD-L1.

Main Results:

  • TMEM199 was confirmed to localize in the nucleus.
  • Nuclear TMEM199 was found to regulate PD-L1 (CD274) mRNA levels.
  • TMEM199 binds to transcription factors including IFNGR1, IRF1, MTMR9, KAT8, and Trim28, promoting PD-L1 expression.

Conclusions:

  • TMEM199's nuclear localization is a key aspect of its function.
  • TMEM199 plays a significant role in regulating the tumor immune microenvironment via PD-L1 modulation.
  • This study uncovers TMEM199 as a novel regulator of immune responses in cancer.
Keywords:
Molecular biologyMolecular medicine

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