Inal, Jameel M;
Hristova, Mariya;
Lange, Sigrun;
(2022)
A Pilot Study on Peptidylarginine Deiminases and Protein Deimination in Animal Cancers across Vertebrate Species.
International Journal Molecular Sciences
, 23
(15)
, Article 8697. 10.3390/ijms23158697.
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Abstract
PADs are a group of calcium-dependent enzymes that play key roles in inflammatory pathologies and have diverse roles in cancers. PADs cause irreversible post-translational modification of arginine to citrulline, leading to changes in protein function in different cellular compartments. PAD isozyme diversity differs throughout phylogeny in chordates, with five PAD isozymes in mammals, three in birds, and one in fish. While the roles for PADs in various human cancers are mounting (both in regards to cancer progression and epigenetic regulation), investigations into animal cancers are scarce. The current pilot-study therefore aimed at assessing PAD isozymes in a range of animal cancers across the phylogeny tree. In addition, the tissue samples were assessed for total protein deimination and histone H3 deimination (CitH3), which is strongly associated with human cancers and also indicative of gene regulatory changes and neutrophil extracellular trap formation (NETosis). Cancers were selected from a range of vertebrate species: horse, cow, reindeer, sheep, pig, dog, cat, rabbit, mink, hamster, parrot, and duck. The cancers chosen included lymphoma, kidney, lung, testicular, neuroendocrine, anaplastic, papilloma, and granulosa cell tumour. Immunohistochemical analysis revealed that CitH3 was strongly detected in all of the cancers assessed, while pan-deimination detection was overall low. Both PAD2 and PAD3 were the most predominantly expressed PADs across all of the cancers assessed, while PAD1, PAD4, and PAD6 were overall expressed at lower, albeit varying, levels. The findings from this pilot study provide novel insights into PAD-mediated roles in different cancers across a range of vertebrate species and may aid in the understanding of cancer heterogeneity and cancer evolution.
Type: | Article |
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Title: | A Pilot Study on Peptidylarginine Deiminases and Protein Deimination in Animal Cancers across Vertebrate Species |
Location: | Switzerland |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.3390/ijms23158697 |
Publisher version: | https://www.mdpi.com/1422-0067/23/15/8697# |
Language: | English |
Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
Keywords: | Cancer, cancer evolution, deiminated histone H3 (CitH3), deimination/citrullination, peptidylarginine deiminase (PAD), phylogeny, Animals, Citrullination, Dogs, Epigenesis, Genetic, Histones, Horses, Humans, Isoenzymes, Mammals, Neoplasms, Pilot Projects, Protein Processing, Post-Translational, Protein-Arginine Deiminases, Rabbits, Sheep, Swine, Vertebrates |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences |
URI: | https://discovery.ucl.ac.uk/id/eprint/10154246 |
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