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
Hauptverfasser: Zhang, Pin, Nakatsukasa, Hiroko, Tu, Eric, Kasagi, Shimpei, Cui, Kairong, Ishikawa, Masaki, Konkel, Joanne E., Maruyama, Takashi, Wei, Gang, Abbatiello, Brittany, Wang, Zhao-Qi, Zhao, Keji, Chen, WanJun
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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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2013-05-503250