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

Summary: The function of transmembrane protein 199 (TMEM199) in cancer development has rarely been studied thus far. We report the nuclear localization of the TMEM199 protein and further analyzed the truncated fractions that mediate its nuclear localization. Cut&Tag assay globally explores the n...

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Main Authors: Wulin You, Hue Luu, Meili Li, Zhiyu Chen, Fangchao Li, Yanfei Zhang, Mingsheng Cai, Tong-chuan He, Jingjing Li
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004224027123
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author Wulin You
Hue Luu
Meili Li
Zhiyu Chen
Fangchao Li
Yanfei Zhang
Mingsheng Cai
Tong-chuan He
Jingjing Li
author_facet Wulin You
Hue Luu
Meili Li
Zhiyu Chen
Fangchao Li
Yanfei Zhang
Mingsheng Cai
Tong-chuan He
Jingjing Li
author_sort Wulin You
collection DOAJ
description Summary: The function of transmembrane protein 199 (TMEM199) in cancer development has rarely been studied thus far. We report the nuclear localization of the TMEM199 protein and further analyzed the truncated fractions that mediate its nuclear localization. Cut&Tag assay globally explores the nuclear-located TMEM199 functions and tests its influence on the immune checkpoint PD-L1 in vitro and in vivo. Nuclear-located TMEM199 regulates PD-L1 mRNA levels by binding to transcription factors such as IFNGR1, IRF1, MTMR9, and Trim28, which all promote PD-L1 mRNA expression. Our study demonstrates the nuclear localization of TMEM199 and its immune regulation functions in cancer development. We uncovered the nuclear localization of TMEM199. TMEM199 is involved in CD274 mRNA gene expression by the transcriptional regulation of the upstream transcription factors or cofactors of CD274, such as IFNGR1, IRF1, MTMR9, KAT8, and Trim28. The nuclear-located TMEM199 is reported to address the tumor immune microenvironment commanding function.
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institution Kabale University
issn 2589-0042
language English
publishDate 2024-12-01
publisher Elsevier
record_format Article
series iScience
spelling doaj-art-08d3b3af027d4d0bbea0ab76b5f9c9bc2024-12-22T05:29:30ZengElsevieriScience2589-00422024-12-012712111485Nuclear transmembrane protein 199 promotes immune escapes by up-regulating programmed death ligand 1Wulin You0Hue Luu1Meili Li2Zhiyu Chen3Fangchao Li4Yanfei Zhang5Mingsheng Cai6Tong-chuan He7Jingjing Li8Department of Orthopedics, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, Jiangsu Province, China; Jiangsu CM Clinical Innovation Center of Degenerative Bone & Joint Disease, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, Jiangsu Province, China; Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USAMolecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USAState Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaDepartment of Orthopedics, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, Jiangsu Province, China; Jiangsu CM Clinical Innovation Center of Degenerative Bone & Joint Disease, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, Jiangsu Province, ChinaAffiliated Hospital, School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China; Jinming Yu Academician Workstation of Oncology, Shandong Second Medical University, Weifang, Shandong, ChinaAffiliated Hospital, School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China; Jinming Yu Academician Workstation of Oncology, Shandong Second Medical University, Weifang, Shandong, ChinaState Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ChinaMolecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA; Corresponding authorAffiliated Hospital, School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China; Jinming Yu Academician Workstation of Oncology, Shandong Second Medical University, Weifang, Shandong, China; Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA; Corresponding authorSummary: The function of transmembrane protein 199 (TMEM199) in cancer development has rarely been studied thus far. We report the nuclear localization of the TMEM199 protein and further analyzed the truncated fractions that mediate its nuclear localization. Cut&Tag assay globally explores the nuclear-located TMEM199 functions and tests its influence on the immune checkpoint PD-L1 in vitro and in vivo. Nuclear-located TMEM199 regulates PD-L1 mRNA levels by binding to transcription factors such as IFNGR1, IRF1, MTMR9, and Trim28, which all promote PD-L1 mRNA expression. Our study demonstrates the nuclear localization of TMEM199 and its immune regulation functions in cancer development. We uncovered the nuclear localization of TMEM199. TMEM199 is involved in CD274 mRNA gene expression by the transcriptional regulation of the upstream transcription factors or cofactors of CD274, such as IFNGR1, IRF1, MTMR9, KAT8, and Trim28. The nuclear-located TMEM199 is reported to address the tumor immune microenvironment commanding function.http://www.sciencedirect.com/science/article/pii/S2589004224027123Molecular biologyMolecular medicine
spellingShingle Wulin You
Hue Luu
Meili Li
Zhiyu Chen
Fangchao Li
Yanfei Zhang
Mingsheng Cai
Tong-chuan He
Jingjing Li
Nuclear transmembrane protein 199 promotes immune escapes by up-regulating programmed death ligand 1
iScience
Molecular biology
Molecular medicine
title Nuclear transmembrane protein 199 promotes immune escapes by up-regulating programmed death ligand 1
title_full Nuclear transmembrane protein 199 promotes immune escapes by up-regulating programmed death ligand 1
title_fullStr Nuclear transmembrane protein 199 promotes immune escapes by up-regulating programmed death ligand 1
title_full_unstemmed Nuclear transmembrane protein 199 promotes immune escapes by up-regulating programmed death ligand 1
title_short Nuclear transmembrane protein 199 promotes immune escapes by up-regulating programmed death ligand 1
title_sort nuclear transmembrane protein 199 promotes immune escapes by up regulating programmed death ligand 1
topic Molecular biology
Molecular medicine
url http://www.sciencedirect.com/science/article/pii/S2589004224027123
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