ArticleNature2018
The protein histidine phosphatase LHPP is a tumour suppressor.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 263 citations in OpenAlex.
- Interaction of Bacterial Histidine Phosphatase SixA With Phosphocarrier Protein NPr and Phosphohistidine Analogs.Journal of molecular biology · 2026Article
- Intratumoral Mycobacterium abscessus promotes cytidine deaminase mutagenesis in non-small cell lung cancer.Signal transduction and targeted therapy · 2026Article
- Improving heterologous protein production by modulating ROS homeostasis in Nicotiana benthamiana.Molecular horticulture · 2026Article
- Advances in signaling pathway networks involving LHPP in various diseases.Molecular and cellular biochemistry · 2026Review
- LHPP expression in triple-negative breast cancer promotes tumor growth and metastasis by modulating the tumor microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Using phage display for rational engineering of a higher-affinity humanized 3' phosphohistidine-specific antibody.Communications chemistry · 2025Article
- Decoding protein N-phosphorylation functionality and sequence patterns.Briefings in bioinformatics · 2025Article
- Are you having a LaPh? Diverse roles of Labile Phosphorylation in mammalian cells.Biochemical Society transactions · 2025Review
- Post-translational modifications in hepatocellular carcinoma: mechanisms and therapeutic potential.Medical oncology (Northwood, London, England) · 2025Review
- Proteomics in pancreatic cancer.Biomarker research · 2025Review
- RNAa: Mechanisms, therapeutic potential, and clinical progress.Molecular therapy. Nucleic acids · 2025Review
- Targeting LHPP in neoadjuvant chemotherapy resistance of gastric cancer: insights from single-cell and multi-omics data on tumor immune microenvironment and stemness characteristics.Cell death & disease · 2025Article
- LHPP-P38 MAPK/ERK-ETS1 Axis Negative Feedback Signaling Restrains Progression in Breast Cancer.Cancer science · 2025Article
- Acetylation: a new target for protein degradation in cancer.Trends in cancer · 2025Review
- LHPP Attenuates Lipid Dysfunction of Uveal Melanoma by Relieving the Histidine Phosphorylation of ACO2.Research (Washington, D.C.) · 2025Article
- Identification of transglutaminase 2 mediated polyaminated proteins in a hepatocellular cancer cell line.Computational and structural biotechnology journal · 2025Article
- Research Progress of SGLT2 Inhibitors in Cancer Treatment.Drug design, development and therapy · 2025Review
- Roles of nucleotide metabolism in pancreatic cancer.Frontiers in immunology · 2025Review
- Deciphering STAT3's negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysis.Molecular medicine (Cambridge, Mass.) · 2024Article
- Histidine phosphatase-ferroptosis crosstalk modulation for efficient hepatocellular carcinoma treatment.Journal of nanobiotechnology · 2024Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
Histidine phosphorylation, the so-called hidden phosphoproteome, is a poorly characterized post-translational modification of proteins. Here we describe a role of histidine phosphorylation in tumorigenesis. Proteomic analysis of 12 tumours from an mTOR-driven hepatocellular carcinoma mouse model revealed that NME1 and NME2, the only known mammalian histidine kinases, were upregulated. Conversely, expression of the putative histidine phosphatase LHPP was downregulated specifically in the tumours. We demonstrate that LHPP is indeed a protein histidine phosphatase. Consistent with these observations, global histidine phosphorylation was significantly upregulated in the liver tumours. Sustained, hepatic expression of LHPP in the hepatocellular carcinoma mouse model reduced tumour burden and prevented the loss of liver function. Finally, in patients with hepatocellular carcinoma, low expression of LHPP correlated with increased tumour severity and reduced overall survival. Thus, LHPP is a protein histidine phosphatase and tumour suppressor, suggesting that deregulated histidine phosphorylation is oncogenic.
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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.