The protein histidine phosphatase LHPP is a tumour suppressor

The protein histidine phosphatase LHPP is a tumour suppressor Nature 555, 7698 (2018). doi:10.1038/nature26140 Authors: Sravanth K. Hindupur, Marco Colombi, Stephen R. Fuhs, Matthias S. Matter, Yakir Guri, Kevin Adam, Marion Cornu, Salvatore Piscuoglio, Charlotte K. Y. Ng, Charles Betz, Dritan Liko, Luca Quagliata, Suzette Moes, Paul Jenoe, Luigi M. Terracciano, Markus H. Heim, Tony Hunter & Michael N. Hall 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, sugges...
Source: Nature - Category: Research Authors: Tags: Letter Source Type: research