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Dimerization of translationally controlled tumor protein is essential for its cytokine-like activity

Title
Dimerization of translationally controlled tumor protein is essential for its cytokine-like activity
Authors
Kim M.Min H.J.Won H.Y.Park H.Lee J.-C.Park H.-W.Chung J.Hwang E.S.Lee K.
Ewha Authors
이경림황은숙
SCOPUS Author ID
이경림scopus; 황은숙scopus
Issue Date
2009
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
vol. 4, no. 7
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Background: Translationally Controlled Tumor Protein (TCTP) found in nasal lavage fluids of allergic patients was named IgE-dependent histamine-releasing factor (HRF). Human recombinant HRF (HrHRF) has been recently reported to be much less effective than HRF produced from activated mononuclear cells (HRFmn). Methods and Findings: We found that only NH2-terminal truncated, but not C-terminal truncated, TCTP shows cytokine releasing activity compared to full-length TCTP. Interestingly, only NH2-terminal truncated TCTP, unlike full-length TCTP, forms dimers through intermolecular disulfide bonds. We tested the activity of dimerized full-length TCTP generated by fusing it to rabbit Fc region. The untruncated-full length protein (Fc-HrTCTP) was more active than HrTCTP in BEAS-2B cells, suggesting that dimerization of TCTP, rather than truncation, is essential for the activation of TCTP in allergic responses. We used confocal microscopy to evaluate the affinity of TCTPs to its putative receptor. We detected stronger fluorescence in the plasma membrane of BEAS-2B cells incubated with Del-N11TCTP than those incubated with rat recombinant TCTP (RrTCTP). Allergenic activity of Del-N11TCTP prompted us to see whether the NH2-terminal truncated TCTP can induce allergic airway inflammation in vivo. While RrTCTP had no influence on airway inflammation, Del-N11TCTP increased goblet cell hyperplasia in both lung and rhinal cavity. The dimerized protein was found in sera from allergic patients, and bronchoalveolar lavage fluids from airway inflamed mice. Conclusions: Dimerization of TCTP seems to be essential for its cytokine-like activity. Our study has potential to enhance the understanding of pathogenesis of allergic disease and provide a target for allergic drug development. © 2009 Kim et al.
DOI
10.1371/journal.pone.0006464
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약학대학 > 약학과 > Journal papers
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