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Fundamental research

04 - 04 - 2018

Histidine Phosphorylation: a new target against cancer

Studies in mice have found that the LHPP protein present in humans can stop the growth of tumors.
In 1979 Tony Hunter discovered that the phosphorylation (addition of a phosphate group) of the amino acid tyrosine on certain proteins could promote cancer. From this discovery came the family of anticancer drugs called tyrosine kinase inhibitors, including Glivec.
Today a team of researchers has studied the phosphorylation of histidine in a mouse model of liver cancer. The team has just published the results:
• histidine kinases NME1 and NME2 (which add a phosphate group) are increased in the presence of cancer
• Histidine phosphatase LHPP (which removes a phosphate group) is totally absent from the tumor tissue
• the rate of phosphorylated proteins on histidines is higher in tumor tissue than in healthy tissue
- The introduction of LHPP activity in mice that naturally developed tumors, prevents the development of tumors.
LHPP is a tumor suppressing factor.
Studies in human liver tumors showed high levels of NME1 and 2, and decreased LHPP. A database of different human cancers has shown that in many liver cancers the level of LHPP was decreased and the rate correlated with the severity of the disease and life expectancy.
Phosphorylation of histidine and LHPP could be new therapeutic targets for cancer control.