The PTPRT pseudo-phosphatase domain is a denitrase

Zhao, Y.; Zhao, S.; Hao, Y.; Wang, B.; Zhang, P.; Feng, X.; Chen, Y.; Song, J.; Mieyal, J.; Markowitz, S.; Ewing, R.; Conlon, R.; Miyagi, M.; Wang, Z.

doi:10.1101/238980

bioRxiv · 10.1101/238980

The PTPRT pseudo-phosphatase domain is a denitrase

Zhao, Y.·Zhao, S.·Hao, Y.·Wang, B.·Zhang, P.·Feng, X.·Chen, Y.·Song, J.·Mieyal, J.·Markowitz, S.·Ewing, R.·Conlon, R.·Miyagi, M.·Wang, Z.

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Abstract

Protein tyrosine nitration occurs under both physiological and pathological conditions1. However, enzymes that remove this protein modification have not yet been identified. Here we report that the pseudo-phosphatase domain of protein tyrosine receptor T (PTPRT) is a denitrase that removes nitro-groups from tyrosine residues in paxillin. PTPRT normally functions as a tumor suppressor and is frequently mutated in a variety of human cancers including colorectal cancer2,3. We demonstrate that some of the tumor-derived mutations located in the pseudophosphatase domain impair the denitrase activity. Moreover, PTPRT mutant mice that inactivate the denitrase activity are susceptible to carcinogen-induced colon tumor formation. This study uncovers a novel enzymatic activity that is involved in tumor suppression.

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Zhao, Y., Zhao, S., Hao, Y., Wang, B., Zhang, P., Feng, X., Chen, Y., Song, J., Mieyal, J., Markowitz, S., Ewing, R., Conlon, R., Miyagi, M., Wang, Z.. 2017-12-22. The PTPRT pseudo-phosphatase domain is a denitrase. https://doi.org/10.1101/238980

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