IFN-γ and TNF-α-induced GBP-1 inhibits epithelial cell proliferation through suppression of β-catenin/TCF signaling
Capaldo CT, Beeman N, Hilgarth RS, Nava P, Louis NA, Naschberger E, Stürzl M, Parkos CA, Nusrat A (2012)
Publication Type: Journal article
Publication year: 2012
Journal
Book Volume: 5
Pages Range: 681-690
Journal Issue: 6
DOI: 10.1038/mi.2012.41
Abstract
Proinflammatory cytokines induce guanylate-binding protein 1 (GBP-1) protein expression in intestinal epithelial tissues. GBP-1 has been described as influencing a number of cellular processes important for epithelial homeostasis, including cell proliferation. However, many questions remain as to the role of GBP-1 in intestinal mucosal homeostasis. We therefore sought to investigate the function of proinflammatory cytokine-induced GBP-1 during intestinal epithelial cell proliferation. Through the use of complementary GBP-1 overexpression and small interfering RNA-mediated knockdown studies, we now show that GBP-1 acts to inhibit pro-mitogenic β-catenin/T cell factor (TCF) signaling. Interestingly, proinflammatory cytokine-induced GBP-1 was found to be a potent suppressor of β-catenin protein levels and β-catenin serine 552 phosphorylation. Neither glycogen synthase kinase 3β nor proteasomal inhibition alleviated GBP-1-mediated suppression of cell proliferation or β-catenin/TCF signaling, indicating a non-canonical mechanism of β-catenin inhibition. Together, these data show that cytokine-induced GBP-1 retards cell proliferation by forming a negative feedback loop that suppresses β-catenin/TCF signaling. © 2012 Society for Mucosal Immunology.
Authors with CRIS profile
Elisabeth Naschberger
Medizinische Fakultät
Michael Stürzl
Professur für Molekulare und Experimentelle Chirurgie
Involved external institutions
United States (USA) (US)How to cite
APA:
Capaldo, C.T., Beeman, N., Hilgarth, R.S., Nava, P., Louis, N.A., Naschberger, E.,... Nusrat, A. (2012). IFN-γ and TNF-α-induced GBP-1 inhibits epithelial cell proliferation through suppression of β-catenin/TCF signaling. Mucosal Immunology, 5(6), 681-690. https://doi.org/10.1038/mi.2012.41
MLA:
Capaldo, C. T., et al. "IFN-γ and TNF-α-induced GBP-1 inhibits epithelial cell proliferation through suppression of β-catenin/TCF signaling." Mucosal Immunology 5.6 (2012): 681-690.
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