PARP-1 regulates expression of TGF-β receptors in T cells
Transforming growth factor-β (TGF-β) receptors (TβRs) are essential components for TGF-β signal transduction in T cells, yet the mechanisms by which the receptors are regulated remain poorly understood. We show here that Poly(ADP-ribose) polymerase-1 (PARP-1) regulates TGF-β receptor I (TβRI) and II...
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Veröffentlicht in: | Blood 2013-09, Vol.122 (13), p.2224-2232 |
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Sprache: | eng |
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Zusammenfassung: | Transforming growth factor-β (TGF-β) receptors (TβRs) are essential components for TGF-β signal transduction in T cells, yet the mechanisms by which the receptors are regulated remain poorly understood. We show here that Poly(ADP-ribose) polymerase-1 (PARP-1) regulates TGF-β receptor I (TβRI) and II (TβRII) expression in CD4+ T cells and subsequently affects Smad2/3-mediated TGF-β signal transduction. Inhibition of PARP-1 led to the upregulation of both TβRI and TβRII, yet the underlying molecular mechanisms were distinct. PARP-1 selectively bound to the promoter of TβRII, whereas the enzymatic activity of PARP-1 was responsible for the inhibition of TβRI expression. Importantly, inhibition of PARP-1 also enhanced expression of TβRs in human CD4+ T cells. Thus, PARP-1 regulates TβR expression and TGF-β signaling in T cells.
•PARP-1 controls TGF-β receptors on T cells.•PARP-1 regulates Treg generation. |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2013-05-503250 |