ArticleThe Journal of experimental medicine2021
E3 ligase MKRN3 is a tumor suppressor regulating PABPC1 ubiquitination in non-small cell lung cancer.
Open access · greenAbstract read
In one paragraph
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- PABPC1--mRNA stability, protein translation and tumorigenesis.Frontiers in oncology · 2022Pooled it
- Article
- High-throughput screening identifies a critical role of the SPOP-PABPC1 axis in lung adenocarcinoma progression.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The central precocious puberty-associated gene MKRN3 is a tumor suppressor regulating CSDE1 ubiquitination in ovarian cancer.Oncogenesis · 2026Article
- UBE2M as a bridge spanning neddylation and cell cycle regulation in colorectal adenocarcinoma.Experimental & molecular medicine · 2026Article
- Integrated mutational landscape analysis of endometrial stromal sarcoma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeted Protein Degradation in Lung Cancer: The Emerging Role of PROTAC Technology and E3 Ligases.Current medicinal chemistry · 2026Review
- PABPC1 expression in papillary renal cell carcinoma and its significance for survival outcomes.Journal, genetic engineering & biotechnology · 2025Article
- The scaffold protein DLG4 facilitates RNF63-mediated ubiquitination and degradation of STAT3 in non-small cell lung cancer.Cell communication and signaling : CCS · 2025Article
- A novel model of central precocious puberty disease: Paternal MKRN3 gene-modified rabbit.Animal models and experimental medicine · 2025Article
- Stage-Specific Tumoral Gene Expression Profiles of Black and White Patients with Colon Cancer.Annals of surgical oncology · 2025Article
- TC2N maintains stem cell-like characteristics to accelerate lung carcinogenesis by blockade of dual specificity protein phosphatase 3.Cell & bioscience · 2025Article
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Significance of circular RNAs in regulating protein ubiquitination for malignant tumor progression.Frontiers in immunology · 2025Review
- Altered methylation of imprinted genes in neuroblastoma: implications for prognostic refinement.Journal of translational medicine · 2024Article
- Crosstalk among Alternative Polyadenylation, Genetic Variants and Ubiquitin Modification Contribute to Lung Adenocarcinoma Risk.International journal of molecular sciences · 2024Article
- Advances of E3 ligases in lung cancer.Biochemistry and biophysics reports · 2024Review
- Energy stress-induced circDDX21 promotes glycolysis and facilitates hepatocellular carcinogenesis.Cell death & disease · 2024Article
- Molecular mechanism of radiation tolerance in lung adenocarcinoma cells using single-cell RNA sequencing.Journal of cellular and molecular medicine · 2024Article
- Malignancies in Prader-Willi Syndrome: Results From a Large International Cohort and Literature Review.The Journal of clinical endocrinology and metabolism · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 9 institutions in 2 countries.
Ke Li *Chinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0003-2671-926X
Xufen Zheng *Chinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0002-0081-8676
Hua Tang *Department of Thoracic Surgery, Changzheng Hospital, Shanghai, China.ORCID 0000-0002-7132-960X
Yuan-Sheng Zang *Department of Medical Oncology, Changzheng Hospital, Shanghai, China.ORCID 0000-0002-9488-7305
Chunling ZengChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0003-2575-5613
Xiaoxiao LiuChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0003-3773-7455
Yanying ShenDepartment of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.ORCID 0000-0001-9195-2207
Yuzhi PangChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0003-0713-8320
Simin WangChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0001-6135-7546
Feifei XieChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0001-9926-2809
Xiaojing LuChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0001-7628-7245
Yuxiang LuoChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0001-5911-4158
Zhang LiChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0002-0740-6068
Wenbo BiChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0002-5150-4220
Xiaona JiaChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0001-9823-9658
Tao HuangBioinformatics Core, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0003-1975-9693
Rongqiang WeiDepartment of Thoracic Surgery, Changzheng Hospital, Shanghai, China.ORCID 0000-0002-6009-9343
Kenan HuangDepartment of Thoracic Surgery, Changzheng Hospital, Shanghai, China.ORCID 0000-0002-7103-318X
Zihao ChenDepartment of Thoracic Surgery, Changzheng Hospital, Shanghai, China.ORCID 0000-0002-7560-8243
Qingchen ZhuChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0002-9514-0430
Yi HeDepartment of Urology, No. 1 Hospital of Jiaxing, Jiaxing, China.ORCID 0000-0002-1752-8405
Miaoying ZhangDepartment of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China.ORCID 0000-0002-4160-3962
Zhizhan GuDepartment of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT.ORCID 0000-0001-9934-5209
Yichuan XiaoChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0001-7804-6971
Xiaoyang ZhangDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.ORCID 0000-0002-0031-0290
Jonathan A FletcherDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.ORCID 0000-0002-5109-2588
Yuexiang WangChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health-Changzheng Hospital Joint Center for Translational Medicine, Institutes for Translational Medicine, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0003-3229-5467
Chinese Academy of Sciences · CNShanghai Changzheng Hospital · CNShanghai Institute of Nutrition and Health · CNAlbert Einstein College of Medicine · USBrigham and Women's Hospital · USChildren's Hospital of Fudan University · CNFirst Hospital of Jiaxing · CNShanghai Jiao Tong University · CNUniversity of Utah · US
Funding
No grant is acknowledged in the PubMed record.
Abstract
Central precocious puberty (CPP), largely caused by germline mutations in the MKRN3 gene, has been epidemiologically linked to cancers. MKRN3 is frequently mutated in non-small cell lung cancers (NSCLCs) with five cohorts. Genomic MKRN3 aberrations are significantly enriched in NSCLC samples harboring oncogenic KRAS mutations. Low MKRN3 expression levels correlate with poor patient survival. Reconstitution of MKRN3 in MKRN3-inactivated NSCLC cells directly abrogates in vitro and in vivo tumor growth and proliferation. MKRN3 knockout mice are susceptible to urethane-induced lung cancer, and lung cell-specific knockout of endogenous MKRN3 accelerates NSCLC tumorigenesis in vivo. A mass spectrometry-based proteomics screen identified PABPC1 as a major substrate for MKRN3. The tumor suppressor function of MKRN3 is dependent on its E3 ligase activity, and MKRN3 missense mutations identified in patients substantially compromise MKRN3-mediated PABPC1 ubiquitination. Furthermore, MKRN3 modulates cell proliferation through PABPC1 nonproteolytic ubiquitination and subsequently, PABPC1-mediated global protein synthesis. Our integrated approaches demonstrate that the CPP-associated gene MKRN3 is a tumor suppressor.
Indexed as
UbiquitinationAmino Acid SequenceAnimalsCarcinogenesisCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationHEK293 CellsHumansLung NeoplasmsMiceMice, Inbred C57BLMice, KnockoutMutationPoly(A)-Binding Protein IProtein BindingKRAS protein, humanMKRN3 protein, humanMkrn3 protein, mousePoly(A)-Binding Protein IProto-Oncogene Proteins p21(ras)Tumor Suppressor ProteinsUbiquitin-Protein LigasesUrethane
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.