Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer Pathogenesis
The peptidylarginine deiminases (PADs) are a family of posttranslational modification enzymes that catalyze the conversion of positively charged protein-bound arginine and methylarginine residues to the uncharged, nonstandard amino acid citrulline. This enzymatic activity is referred to as citrullin...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Biochemistry Research International |
| Online Access: | http://dx.doi.org/10.1155/2012/895343 |
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| author | Sunish Mohanan Brian D. Cherrington Sachi Horibata John L. McElwee Paul R. Thompson Scott A. Coonrod |
| author_facet | Sunish Mohanan Brian D. Cherrington Sachi Horibata John L. McElwee Paul R. Thompson Scott A. Coonrod |
| author_sort | Sunish Mohanan |
| collection | DOAJ |
| description | The peptidylarginine deiminases (PADs) are a family of posttranslational modification enzymes that catalyze the conversion of positively charged protein-bound arginine and methylarginine residues to the uncharged, nonstandard amino acid citrulline. This enzymatic activity is referred to as citrullination or, alternatively, deimination. Citrullination can significantly affect biochemical pathways by altering the structure and function of target proteins. Five mammalian PAD family members (PADs 1–4 and 6) have been described and show tissue-specific distribution. Recent reviews on PADs have focused on their role in autoimmune diseases. Here, we will discuss the potential role of PADs in tumor progression and tumor-associated inflammation. In the context of cancer, increasing clinical evidence suggests that PAD4 (and possibly PAD2) has important roles in tumor progression. The link between PADs and cancer is strengthened by recent findings showing that treatment of cell lines and mice with PAD inhibitors significantly suppresses tumor growth and, interestingly, inflammatory symptoms. At the molecular level, transcription factors, coregulators, and histones are functional targets for citrullination by PADs, and citrullination of these targets can affect gene expression in multiple tumor cell lines. Next generation isozyme-specific PAD inhibitors may have therapeutic potential to regulate both the inflammatory tumor microenvironment and tumor cell growth. |
| format | Article |
| id | doaj-art-a9dee133481b43aa87ed16543eb3cb29 |
| institution | Kabale University |
| issn | 2090-2247 2090-2255 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
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| series | Biochemistry Research International |
| spelling | doaj-art-a9dee133481b43aa87ed16543eb3cb292025-02-03T01:23:40ZengWileyBiochemistry Research International2090-22472090-22552012-01-01201210.1155/2012/895343895343Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer PathogenesisSunish Mohanan0Brian D. Cherrington1Sachi Horibata2John L. McElwee3Paul R. Thompson4Scott A. Coonrod5Baker Institute for Animal Health and Department of Biomedical Sciences, Cornell University, Hungerford Hill Road, Ithaca, NY 14853-6401, USADepartment of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USABaker Institute for Animal Health and Department of Biomedical Sciences, Cornell University, Hungerford Hill Road, Ithaca, NY 14853-6401, USABaker Institute for Animal Health and Department of Biomedical Sciences, Cornell University, Hungerford Hill Road, Ithaca, NY 14853-6401, USADepartment of Chemistry, The Scripps Research Institute, FL 33458, USABaker Institute for Animal Health and Department of Biomedical Sciences, Cornell University, Hungerford Hill Road, Ithaca, NY 14853-6401, USAThe peptidylarginine deiminases (PADs) are a family of posttranslational modification enzymes that catalyze the conversion of positively charged protein-bound arginine and methylarginine residues to the uncharged, nonstandard amino acid citrulline. This enzymatic activity is referred to as citrullination or, alternatively, deimination. Citrullination can significantly affect biochemical pathways by altering the structure and function of target proteins. Five mammalian PAD family members (PADs 1–4 and 6) have been described and show tissue-specific distribution. Recent reviews on PADs have focused on their role in autoimmune diseases. Here, we will discuss the potential role of PADs in tumor progression and tumor-associated inflammation. In the context of cancer, increasing clinical evidence suggests that PAD4 (and possibly PAD2) has important roles in tumor progression. The link between PADs and cancer is strengthened by recent findings showing that treatment of cell lines and mice with PAD inhibitors significantly suppresses tumor growth and, interestingly, inflammatory symptoms. At the molecular level, transcription factors, coregulators, and histones are functional targets for citrullination by PADs, and citrullination of these targets can affect gene expression in multiple tumor cell lines. Next generation isozyme-specific PAD inhibitors may have therapeutic potential to regulate both the inflammatory tumor microenvironment and tumor cell growth.http://dx.doi.org/10.1155/2012/895343 |
| spellingShingle | Sunish Mohanan Brian D. Cherrington Sachi Horibata John L. McElwee Paul R. Thompson Scott A. Coonrod Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer Pathogenesis Biochemistry Research International |
| title | Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer Pathogenesis |
| title_full | Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer Pathogenesis |
| title_fullStr | Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer Pathogenesis |
| title_full_unstemmed | Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer Pathogenesis |
| title_short | Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer Pathogenesis |
| title_sort | potential role of peptidylarginine deiminase enzymes and protein citrullination in cancer pathogenesis |
| url | http://dx.doi.org/10.1155/2012/895343 |
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