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The protein histidine phosphatase LHPP is a tumour suppressor

Hindupur, Sravanth K. and Colombi, Marco and Fuhs, Stephen R. and Matter, Matthias S. and Guri, Yakir and Adam, Kevin and Cornu, Marion and Piscuoglio, Salvatore and Ng, Charlotte K. Y. and Betz, Charles and Liko, Dritan and Quagliata, Luca and Moes, Suzette and Jenoe, Paul and Terracciano, Luigi M. and Heim, Markus H. and Hunter, Tony and Hall, Michael N.. (2018) The protein histidine phosphatase LHPP is a tumour suppressor. Nature, 555. pp. 678-682.

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
ISSN:0028-0836
e-ISSN:1476-4687
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:20 Apr 2018 11:32
Deposited On:06 Apr 2018 11:22

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