Citrullination: A posttranslational modification in health and disease

György, Bence; Tóth, Erzsébet; Tarcsa, Edit; Falus, András; Buzás, Edit I.

doi:10.1016/j.biocel.2006.03.008

Cited by 427 publications

(471 citation statements)

References 90 publications

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“…Histone methylation, phosphorylation and acetylation are reversible processes that are regulated by histone-modifying enzymes 34 . In contrast, citrullination is a chemically stable modification, and decitrullination enzymes have not yet been discovered 35 . Therefore, histone citrullination is considered to be an irreversible cellular process.…”

Section: Discussionmentioning

confidence: 99%

Regulation of histone modification and chromatin structure by the p53–PADI4 pathway

et al. 2012

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Histone proteins are modified in response to various external signals; however, their mechanisms are still not fully understood. Citrullination is a post-transcriptional modification that converts arginine in proteins into citrulline. Here we show in vivo and in vitro citrullination of the arginine 3 residue of histone H4 (cit-H4R3) in response to DnA damage through the p53-PADI4 pathway. We also show DnA damage-induced citrullination of Lamin C. Cit-H4R3 and citrullinated Lamin C localize around fragmented nuclei in apoptotic cells. Ectopic expression of PADI4 leads to chromatin decondensation and promotes DnA cleavage, whereas Padi4 − / − mice exhibit resistance to radiation-induced apoptosis in the thymus. Furthermore, the level of cit-H4R3 is negatively correlated with p53 protein expression and with tumour size in non-small cell lung cancer tissues. our findings reveal that cit-H4R3 may be an 'apoptotic histone code' to detect damaged cells and induce nuclear fragmentation, which has a crucial role in carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Regulation of histone modification and chromatin structure by the p53–PADI4 pathway

et al. 2012

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“…Although the human peptidylarginine deiminase family contains five isotypes (PAD 1, 2, 3, 4/5 and 6) with tissue specific expression [15], there is a paucity of information on the P. gingivalis PPAD(s) infecting different tissues and cells [16]. Protein citrullination is important for many normal physiological processes such as epithelial terminal differentiation, regulation of gene expression, apoptosis, and inflammation [14,15,17]. However, the posttranslational modification involving the citrullination process can affect the function of several signalling molecules as well as protein structures and functions.…”

Section: Introductionmentioning

confidence: 99%

“…On citrullination by PPAD, C5a loses this function [18]. It is not surprising therefore that an increased citrullination of cytoskeletal filaments and PAD enzymes have been found in numerous chronic inflammatory and autoimmune diseases like AD, RA, and multiple sclerosis (MS), respectively [15,19]. Owing to their similar etiologies, PPAD deserves some consideration as an extrinsic antigen in the pathogenesis of RA and MS, thus contributing to autoimmune processes.…”

Section: Introductionmentioning

confidence: 99%

“…Matsuomi et al [65] found an abnormal accumulation of citrullinated proteins and an increase of the PAD2 content in the hippocampi of AD patients. The most over-citrullinated proteins in AD were structural proteins such as vimentin, MBP and GFAP [15]. Neurodegenerative processes following P. gingivalis infection in animal models are currently under-investigated and further research is essential to determine PD-related causal factors in AD.…”

Section: Introductionmentioning

confidence: 99%

“…During neurodegenerative processes, it has been hypothesized that a higher concentration of Ca ++ activates citrullination [15] but, P. gingivalis LPS and intact citrulline constitute potential contributory factors [68]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer’s disease

Olsen

Singhrao

Potempa

2018

Journal of Oral Microbiology

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Periodontitis, rheumatoid arthritis (RA), atherosclerosis (AS), and Alzheimer’s disease (AD) are examples of complex human diseases with chronic inflammatory components in their etiologies. The initial trigger of inflammation that progresses to these diseases remains unresolved. Porphyromonas gingivalis is unique in its ability to secrete the P. gingivalis-derived peptidyl arginine deiminase (PPAD) and consequently offers a plausible and exclusive link to these diseases through enzymatic conversion of arginine to citrulline. Citrullination is a post-translational enzymatic modification of arginine residues in proteins formed as part of normal physiological processes. However, PPAD has the potential to modify self (bacterial) and host proteins by deimination of arginine amino acid residues, preferentially at the C-terminus. Migration of P. gingivalis and/or its secreted PPAD into the bloodstream opens up the possibility that this enzyme will citrullinate proteins at disparate body sites. Citrullination is associated with the pathogenesis of multifactorial diseases such as RA and AD, which have an elusive external perpetrator as they show epidemiological associations with periodontitis. Therefore, PPAD deserves some prominence as an external antigen, in at least, a subset of RA and AD cases, with as yet unidentified, immune/genetic vulnerabilities.

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Periodontitis and Systemic Diseases

Vaithilingam

Baharuddin

2023

Immunology for Dentistry

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Citrullination: A posttranslational modification in health and disease

Cited by 427 publications

References 90 publications

Regulation of histone modification and chromatin structure by the p53–PADI4 pathway

Regulation of histone modification and chromatin structure by the p53–PADI4 pathway

Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer’s disease

Periodontitis and Systemic Diseases

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