ArticleNature communications2026
TRIM21-mediated ubiquitination of PARP1 regulated by the PI3K/AKT-STAT5A axis suppresses small cell lung cancer.
Guozhen Cao, Gongfeng Li, Xiaolin Wang, Tengfei Zhang, Xinhuang Yao, Peng Hou, Jiahui Zhang, Xiaopeng Guo, Jiarong Wang, Li Xiang and 3 more
Abstract read
In one paragraphArticle in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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What it found
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4 · The recordCorrections and comments
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5 · Who and what moneyAuthors and funding
13 authors.
Guozhen Cao *The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, China.ORCID 0000-0002-0213-7153 Gongfeng Li *The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, China.ORCID 0009-0006-8488-1053 Tengfei ZhangKey Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
Xinhuang YaoThe Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, China.
Peng HouThe Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, China.
Jiahui ZhangThe Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, China.ORCID 0000-0002-2013-0289 Xiaopeng GuoSchool of Life Science and Engineering, Lanzhou University of Technology, Lanzhou, China.
Jiarong WangHigh Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, China.
Li XiangThe Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, China.ORCID 0000-0002-7164-0588 Hongbin JiKey Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0003-0891-6390 Chenchen GuoKey Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China. guochenchen2014@sibcb.ac.cn.ORCID 0000-0003-2346-9808 Wenchu LinThe Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, China. linwenchu@ustc.edu.cn.ORCID 0000-0001-6141-1725 Funding
China Postdoctoral Science Foundation 2024M753095National Natural Science Foundation of China (National Science Foundation of China) 82303091National Natural Science Foundation of China (National Science Foundation of China) 82573833Shenzhen Science and Technology Innovation Commission JCYJ20250604180129038
6 · The paper itselfAbstract
Abnormal accumulation of Poly(ADP-ribose) polymerase 1 (PARP1) promotes cancer progression, yet its stabilization mechanisms remain unclear. Here, we identify E3 ubiquitin ligase tripartite motif-containing 21 (TRIM21) as a PARP1-binding partner. PARP1 interacts directly with TRIM21 via its 662-908 domain, while the PRY-SPRY domain of TRIM21 is essential for this binding. TRIM21 facilitates PARP1 polyubiquitination at residue K654, leading to its degradation. In small cell lung cancer (SCLC), TRIM21 is significantly downregulated, and its tumor-suppressive function is partly mediated through the degradation of PARP1, supporting genomic stability. Additionally, the PI3K/AKT pathway transcriptionally suppresses TRIM21 via transcription factor STAT5A, thereby stabilizing PARP1. Importantly, combining the PI3K/AKT inhibitor PKI-587 with the PARP inhibitor BMN673 synergistically inhibits tumor growth across multiple SCLC models, including cell lines, patient-derived organoids, and xenograft models. Collectively, our findings define a "PI3K/AKT-STAT5A-TRIM21-PARP1" axis critical for SCLC progression and propose its dual inhibition as a promising therapeutic strategy.
Indexed as
Lung NeoplasmsPhosphatidylinositol 3-KinasesPoly (ADP-Ribose) Polymerase-1Proto-Oncogene Proteins c-aktSmall Cell Lung CarcinomaSTAT5 Transcription FactorAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMiceMice, NudeSignal TransductionTRIM21 ProteinUbiquitinationPARP1 protein, humanPhosphatidylinositol 3-KinasesPoly (ADP-Ribose) Polymerase-1Proto-Oncogene Proteins c-aktSTAT5 Transcription FactorTRIM21 Protein
Identifiers
PMID42315836
PMCPMC13434705
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