Protein citrullination by bacterial PPAD in oral cancer

Host cell protein citrullination by the periodontal pathogen Porphyromonas gingivalis 

About the group

Porphyromonas gingivalis, an anaerobic bacterium of the human oral cavity, is involved in periodontal diseases and promotion of oral cancers. However, the specific mechanisms by which it targets host cells intracellularly and contributes to cancer progression remain incompletely understood. Porphyromonas peptidylarginine deiminase (PPAD) is a virulence factor unique to this bacterium. PPAD specifically targets arginine residues in polypeptides, converting and neutralizing its positive charge in a process called citrullination. Citrullination is a post-translational modification, potentially affecting the folding of the targeted protein. Histone and several cytoskeletal proteins (vimentin, actin, keratin, tubulin...) are known targets for citrullination reactions which lead to chromatin structure and transcriptional changes when histones are concerned. Such dysregulation may potentially contribute to tumorigenesis and cancer promotion, depending on the targeted genomic areas. The objective of this project was to evaluate and assess the physiological role of citrullination by PPAD in oral cavity-derived CaLH3 cells.

By using a combination of transient transfection of PPAD into CaLH3 cells and subcellular fractionation to separate the cellular compartments, we investigate the presence of PPAD within different cellular compartments and subcompartments. Protein citrullination is also investigated to determine a potential citrullinating role of PPAD after transfection. Western blot results are relatively quantitated by ImageJ and localization of PPAD in whole cells is also determined by laser scanning confocal imaging.

 

Cooperation

  • Ass. Prof. Morten Enersen (Institute of Oral Biology, UiO)
  • Ass. Prof. Roger Junges (Institute of Oral Biology, UiO)
  • Prof. Fernanda Petersen (Institute of Oral Biology, UiO)
  • Ass. Prof. Roger Simm (Institute of Oral Biology, UiO)
Published Aug. 14, 2018 11:20 AM - Last modified June 20, 2023 1:34 PM

Contact

Institute of Oral Biology
Domus Odontologica
Sognsvannsveien 10
0372 Oslo

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