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 (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.
Mucosal Immunology Section, Oral Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD;
Pin
P
Zhang
Hiroko
H
Nakatsukasa
Eric
E
Tu
Shimpei
S
Kasagi
Kairong
K
Cui
Masaki
M
Ishikawa
Joanne E
JE
Konkel
Takashi
T
Maruyama
Gang
G
Wei
Brittany
B
Abbatiello
Zhao-Qi
ZQ
Wang
Keji
K
Zhao
WanJun
W
Chen
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000276:immunology / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D015398:Signal Transduction / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism
D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C499320:PARP1 protein, human; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases