{"database":"iProX","file_versions":[],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Chunyi Zhang"],"species":["Homo Sapiens"],"full_dataset_link":["http://www.iprox.org/page/project.html?id=IPX0016256000"],"submitter_email":["cyzhang@fudan.edu.cn"],"submitter_affiliation":["Fudan University"],"sample_protocol":[""],"repository":["iProX"],"data_protocol":[""],"pubmed_abstract":["Immunotherapy has emerged as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC), but over half of patients fail to benefit, largely due to tumor heterogeneity and a complex tumor microenvironment. Here, we demonstrate that fibrinogen-like protein 1 (FGL1), a recently identified immune checkpoint ligand, is targeted by tripartite motif-containing protein 21 (TRIM21) for proteasomal degradation, thereby enhancing the anti-tumor activity of cytotoxic T lymphocytes (CTLs). We further show that interferon regulatory factor 1 (IRF1) regulates TRIM21 transcription. Artemisinin upregulates the IRF1-TRIM21 axis, promoting FGL1 degradation. In high FGL1 expressed tumors, artemisinin in combination with anti-programmed cell death protein 1 (anti-PD-1) therapy enhances immunotherapeutic efficacy. Clinically, an elevated FGL1/TRIM21 protein ratio is associated with poor prognosis in NSCLC. Collectively, these findings elucidate a post-translational regulatory mechanism of FGL1 in tumor progression and support the development of a rational combination immunotherapy strategy for NSCLC treatment."],"pubmed_title":["Targeting IRF1-TRIM21 axis enhances anti-tumor immunity by promoting ubiquitin-mediated degradation of FGL1 in non-small cell lung cancer."],"pubmed_authors":["Zhang Yuchen Y, Zhou Pingjing P, Guo Yifan Y, Zhang Hongyu H, Zhao Guangyin G, Yin Jun J, Ge Di D, Liu Ronghua R, Gu Jie J, Zhang Chunyi C"],"additional_accession":[]},"is_claimable":false,"name":"Targeting IRF1-TRIM21 axis Enhances Anti-Tumor Immunity by Promoting ubiquitin-mediated degradation of FGL1 in non-small cell lung cancer","description":"Immunotherapy has emerged as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC), but over half of patients fail to benefit, largely due to tumor heterogeneity and a complex tumor microenvironment. Here, we demonstrate that fibrinogen-like protein 1 (FGL1), a recently identified immune checkpoint ligand, is targeted by tripartite motif-containing protein 21 (TRIM21) for proteasomal degradation, thereby enhancing the anti-tumor activity of cytotoxic T lymphocytes (CTLs). We further show that interferon regulatory factor 1 (IRF1) regulates TRIM21 transcription. Artemisinin upregulates the IRF1-TRIM21 axis, promoting FGL1 degradation. In high FGL1 expressed tumors, artemisinin in combination with anti-programmed cell death protein 1 (anti-PD-1) therapy enhances immunotherapeutic efficacy. Clinically, an elevated FGL1/TRIM21 protein ratio is associated with poor prognosis in NSCLC. Collectively, these findings elucidate a post-translational regulatory mechanism of FGL1 in tumor progression and support the development of a rational combination immunotherapy strategy for NSCLC treatment.","dates":{"publication":"Fri Mar 27 00:00:00 GMT 2026"},"accession":"PXD076230","cross_references":{"TAXONOMY":["9606"],"pubmed":["42020516"]}}