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The PTPRT pseudo-phosphatase domain is a denitrase

Yiqing Zhao, Shuliang Zhao, Yujun Hao, View ORCID ProfileBenlian Wang, Peng Zhang, Xiujing Feng, Yicheng Chen, Jing Song, John Mieyal, Sanford Markowitz, Rob M. Ewing, Ronald A. Conlon, Masaru Miyagi, Zhenghe Wang
doi: https://doi.org/10.1101/238980
Yiqing Zhao
1Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
2Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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Shuliang Zhao
3Division of Gastroenterology and Hepatology and Shanghai Institution of Digestive Disease; Shanghai Jiao-Tong University School of Medicine Renji Hospital, 145 Middle Shandong Rd, Shanghai 200001, China
1Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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Yujun Hao
1Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
2Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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Benlian Wang
4Department of Nutrition and Center for Proteomics and Bioinformatics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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  • ORCID record for Benlian Wang
Peng Zhang
1Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
2Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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Xiujing Feng
1Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
2Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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Yicheng Chen
1Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
2Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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Jing Song
4Department of Nutrition and Center for Proteomics and Bioinformatics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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John Mieyal
5Department of Pharmacology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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Sanford Markowitz
1Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
2Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
6Department of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
7Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH 44106
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Rob M. Ewing
8Computational and Systems Biology, School of Biological Sciences, University of Southampton, Southampton SO171BJ, UK
4Department of Nutrition and Center for Proteomics and Bioinformatics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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Ronald A. Conlon
1Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
2Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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Masaru Miyagi
4Department of Nutrition and Center for Proteomics and Bioinformatics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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Zhenghe Wang
1Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
2Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106
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  • For correspondence: zxw22@case.edu
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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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Posted December 22, 2017.
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The PTPRT pseudo-phosphatase domain is a denitrase
Yiqing Zhao, Shuliang Zhao, Yujun Hao, Benlian Wang, Peng Zhang, Xiujing Feng, Yicheng Chen, Jing Song, John Mieyal, Sanford Markowitz, Rob M. Ewing, Ronald A. Conlon, Masaru Miyagi, Zhenghe Wang
bioRxiv 238980; doi: https://doi.org/10.1101/238980
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The PTPRT pseudo-phosphatase domain is a denitrase
Yiqing Zhao, Shuliang Zhao, Yujun Hao, Benlian Wang, Peng Zhang, Xiujing Feng, Yicheng Chen, Jing Song, John Mieyal, Sanford Markowitz, Rob M. Ewing, Ronald A. Conlon, Masaru Miyagi, Zhenghe Wang
bioRxiv 238980; doi: https://doi.org/10.1101/238980

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