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Enhanced DNA damage‐induced p53 peptide phosphorylation and cell‐cycle arrest in Sjögren’s syndrome cells
Author(s) -
Henriksson G.,
Brant M.,
Sallmyr A.,
Fukushima S.,
Manthorpe R.,
Bredberg A.
Publication year - 2002
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2002.00997.x
Subject(s) - dna damage , cell cycle , phosphorylation , cell cycle checkpoint , flow cytometry , biology , microbiology and biotechnology , pathogenesis , cancer research , immunology , cell , dna , biochemistry
Background Cells from primary Sjögren’s syndrome (SS) patients have been reported to show alterations in DNA repair and p53 expression. The DNA‐dependent protein kinase (DNA‐PK) autoantigen may be involved in both of these alterations in relation to cellular DNA damage responses. We conducted this study of cell‐cycle kinetics and p53 to find additional evidence for an abnormal stress response role in the pathogenesis of SS. Design DNA‐dependent protein kinase activity, p53 peptide phosphorylation and p53 protein levels were determined in gamma‐irradiated long‐term T lymphocyte cultures. Cell‐cycle progression of peripheral blood mononuclear cells was analysed with flow cytometry. Results No significant differences in the DNA‐PK activities or p53 protein levels appeared between the SS patients and the healthy individuals. However, patients with the SS hallmark Ro/SS‐A and La/SS‐B autoantibodies showed enhancement of both p53 peptide phosphorylation ( P = 0·036) and G1 cell‐cycle arrest ( P = 0·015) in response to gamma radiation. Conclusions Sjögren’s syndrome cells express an enhanced G1 checkpoint function which may be mediated partly by p53 phosphorylation, suggesting that an abnormal stress response in SS is of relevance for the development of this autoimmune disease.