ArticleCell death & disease2021
USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1.
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Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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55citing papers in PubMed, 1 pooled it
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55 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- The benefit and risk of adding immunotherapy to chemoradiotherapy as the first-line treatment for limited-stage small cell lung cancer: a meta-analysis of randomized controlled trials.World journal of surgical oncology · 2025Pooled it
- Ubiquitin-driven regulation of immune checkpoints in lung cancer: Mechanisms and therapeutic implications (Review).Experimental and therapeutic medicine · 2026Review
- SIRT2-mediated deacetylation activates USP22 catalytic function for PD-L1 protein stabilization and tumor immune escape.The Journal of clinical investigation · 2026Article
- A genome-wide association study identifies Asian-specific genetic susceptibility for epigenetic age acceleration.GeroScience · 2026Article
- USP48 promotes tumour progression through the deubiquitination and stabilization of DBF4 in clear cell renal carcinoma.Cancer cell international · 2026Article
- Linalool targets NR3C2 to inhibit NF-κB-mediated gastric cancer progression.Cell division · 2026Article
- USP5 in cancer: a therapeutic window into metabolism and drug resistance.Journal of translational medicine · 2026Review
- Saikosaponin D and paeoniflorin improve the HCC immune microenvironment via CLCF1/PD-L1 mediated crosstalk between CAFs and tumor cells.Scientific reports · 2026Article
- Ubiquitin-centered post-translational modification crosstalk orchestrates tumor immunity and immunotherapy response.Experimental hematology & oncology · 2026Review
- MGMT upregulation mediates Temozolomide resistance conferred USP5 dependency.Scientific reports · 2026Article
- USP5 inhibition stimulates immunogenic ferroptosis that enhances immunotherapy in diffuse large B-cell lymphoma.Cell communication and signaling : CCS · 2026Article
- Pathological role of deubiquitinating enzymes in lung cancer: recent insights and advances.American journal of cancer research · 2026Review
- LC3-dependent intercellular transfer of phosphorylated STAT1/2 elicits CXCL9+ macrophages and enhances radiation-induced antitumor immunity.The Journal of clinical investigation · 2025Article
- Stabilization of FASN by USP5-mediated deubiquitination promotes hepatocellular carcinoma progression.Oncogenesis · 2025Article
- USP5 regulates ferroptosis in colorectal cancer by targeting the YBX3/SLC7A11 axis through lysosomal degradation.Cell death & disease · 2025Article
- FASN inhibits ferroptosis in breast cancer via USP5 palmitoylation-dependent regulation of GPX4 deubiquitination.Journal of experimental & clinical cancer research : CR · 2025Article
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- TLL1 knockdown attenuates prostate cancer progression by enhancing antitumor immunity.Oncogene · 2025Article
- Spautin-1 inhibits the growth of diffuse large B-cell lymphoma by inducing mitochondrial damage-mediated PANoptosis and anti-tumor immunity.Cancer immunology, immunotherapy : CII · 2025Article
- Opposing regulation of the K63-linked polyubiquitination of RIPK3 by SMURF1 and USP5 in necroptosis.Nature communications · 2025Article
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Authors and funding
18 authors at 8 institutions in 1 country.
Jinghua Pan *Department of Gynecology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, 511518, Guangdong, P.R. China.
Yiting Qiao *Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, NHC Key Laboratory of Combined Multi-organ Transplantation, First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, P. R. China.
Congcong Chen *Department of Medical Biochemistry, Urology and General Surgery, School of Medicine and The First Affiliated Hospital, Jinan University, 510632, Guangzhou, P. R. China.
Hongjing Zang *Department of Pathology, The Second Xiangya Hospital, Central South University, 410011, Changsha, P.R. China.
Xiaojing ZhangDepartment of Gynecology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, 511518, Guangdong, P.R. China.
Feng QiDepartment of Medical Biochemistry, Urology and General Surgery, School of Medicine and The First Affiliated Hospital, Jinan University, 510632, Guangzhou, P. R. China.
Cunjie ChangCollege of Pharmacy, School of Medicine, Department of Hepatology, Institute of Hepatology and Metabolic Diseases, the Affiliated Hospital of Hangzhou Normal University, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, P.R. China.
Fan YangCollege of Pharmacy, School of Medicine, Department of Hepatology, Institute of Hepatology and Metabolic Diseases, the Affiliated Hospital of Hangzhou Normal University, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, P.R. China.
Mengqing SunCollege of Pharmacy, School of Medicine, Department of Hepatology, Institute of Hepatology and Metabolic Diseases, the Affiliated Hospital of Hangzhou Normal University, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, P.R. China.
Shengbin LinDepartment of Medical Biochemistry, Urology and General Surgery, School of Medicine and The First Affiliated Hospital, Jinan University, 510632, Guangzhou, P. R. China.
Quandong TangDepartment of Pathophysiology, Shantou University Medical College, 515041, Shantou, Guangdong, P.R. China.
Lina LiCollege of Pharmacy, School of Medicine, Department of Hepatology, Institute of Hepatology and Metabolic Diseases, the Affiliated Hospital of Hangzhou Normal University, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, P.R. China.
Menglan WangCollege of Pharmacy, School of Medicine, Department of Hepatology, Institute of Hepatology and Metabolic Diseases, the Affiliated Hospital of Hangzhou Normal University, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, P.R. China.
Minjie WuCollege of Pharmacy, School of Medicine, Department of Hepatology, Institute of Hepatology and Metabolic Diseases, the Affiliated Hospital of Hangzhou Normal University, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, P.R. China.
Yongzhu LiuDepartment of Gynecology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, 511518, Guangdong, P.R. China. lyz_1995@yeah.net.ORCID 0000-0002-9205-3841
Caiyong LaiDepartment of Medical Biochemistry, Urology and General Surgery, School of Medicine and The First Affiliated Hospital, Jinan University, 510632, Guangzhou, P. R. China. lcy2015@jnu.edu.cn.ORCID 0000-0003-4679-0944
Jianxiang ChenCollege of Pharmacy, School of Medicine, Department of Hepatology, Institute of Hepatology and Metabolic Diseases, the Affiliated Hospital of Hangzhou Normal University, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, P.R. China. chenjx@hznu.edu.cn.ORCID 0000-0002-8193-191X
Guo ChenDepartment of Medical Biochemistry, Urology and General Surgery, School of Medicine and The First Affiliated Hospital, Jinan University, 510632, Guangzhou, P. R. China. gchen84@jnu.edu.cn.ORCID 0000-0001-8886-1873
Affiliated Hospital of Hangzhou Normal University · CNFirst Affiliated Hospital of Jinan University · CNCentral South University · CNChina Pharmaceutical University · CNFirst Affiliated Hospital Zhejiang University · CNGuangzhou Medical University · CNShantou University · CNSun Yat-sen University · CN
Funding
Guangzhou Municipal Science and Technology Project 202002030451National Natural Science Foundation of China (National Science Foundation of China) 81802338National Natural Science Foundation of China (National Science Foundation of China) 81803523National Natural Science Foundation of China (National Science Foundation of China) 82073042Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation) 2019A1515011247Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation) LR21H160001
Abstract
PD-L1(CD274) is a well-known immunosuppressive molecule, which confers immunoescape features to cancer cells and has become one of the major targets in cancer immunotherapies. Understanding the regulatory mechanisms that control PD-L1 protein expression is important for guiding immune checkpoint blockade therapy. Here, we showed that ubiquitin specific peptidase 5 (USP5) was a novel PD-L1 deubiquitinase in non-small cell lung cancer (NSCLC) cells. USP5 directly interacted with PD-L1 and deubiquitinated PD-L1, therefore enhances PD-L1 protein stability. Meanwhile, USP5 protein levels were highly elevated and positively correlated to PD-L1 levels in NSCLC tissues, and were closely correlated with poor prognosis of these patients. In addition, knockdown of USP5 retarded tumor growth in the Lewis lung carcinoma mouse model. Thus, we identified that USP5 was a new regulator of PD-L1 and targeting USP5 is a promising strategy for cancer therapy.
Indexed as
Disease ProgressionAmino Acid SequenceAnimalsB7-H1 AntigenCarcinoma, Non-Small-Cell LungCell ProliferationDown-RegulationEndopeptidasesFemaleGene DosageHEK293 CellsHumansLung NeoplasmsMaleMiceMice, Inbred C57BLB7-H1 AntigenEndopeptidasesubiquitin isopeptidaseUbiquitin-Specific ProteasesUsp5 protein, mouse
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