PARP-1 regulates expression of TGF-β receptors in T cells.

Pin Zhang; Hiroko Nakatsukasa; Eric Tu; Shimpei Kasagi; Kairong Cui; Masaki Ishikawa; Joanne E Konkel; Takashi Maruyama; Gang Wei; Brittany Abbatiello; Zhao-Qi Wang; Keji Zhao; WanJun Chen

doi:10.1182/blood-2013-05-503250

PARP-1 regulates expression of TGF-β receptors in T cells.

Pin Zhang, Hiroko Nakatsukasa, Eric Tu, Shimpei Kasagi, Kairong Cui, Masaki Ishikawa, Joanne E Konkel, Takashi Maruyama, Gang Wei, Brittany Abbatiello, Zhao-Qi Wang, Keji Zhao, WanJun Chen

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Journal	Blood
Volume	122
Issue number	13
DOIs	https://doi.org/10.1182/blood-2013-05-503250
Publication status	Published - 26 Sept 2013

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title = "PARP-1 regulates expression of TGF-β receptors in T cells.",

abstract = "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.",

author = "Pin Zhang and Hiroko Nakatsukasa and Eric Tu and Shimpei Kasagi and Kairong Cui and Masaki Ishikawa and Konkel, {Joanne E} and Takashi Maruyama and Gang Wei and Brittany Abbatiello and Zhao-Qi Wang and Keji Zhao and WanJun Chen",

note = ", Intramural NIH HHS, United States",

year = "2013",

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day = "26",

doi = "10.1182/blood-2013-05-503250",

language = "English",

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journal = "Blood",

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TY - JOUR

T1 - PARP-1 regulates expression of TGF-β receptors in T cells.

AU - Zhang, Pin

AU - Nakatsukasa, Hiroko

AU - Tu, Eric

AU - Kasagi, Shimpei

AU - Cui, Kairong

AU - Ishikawa, Masaki

AU - Konkel, Joanne E

AU - Maruyama, Takashi

AU - Wei, Gang

AU - Abbatiello, Brittany

AU - Wang, Zhao-Qi

AU - Zhao, Keji

AU - Chen, WanJun

N1 - , Intramural NIH HHS, United States

PY - 2013/9/26

Y1 - 2013/9/26

N2 - 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.

AB - 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.

U2 - 10.1182/blood-2013-05-503250

DO - 10.1182/blood-2013-05-503250

M3 - Article

C2 - 23940283

SN - 1528-0020

SN - 0006-4971

VL - 122

JO - Blood

JF - Blood

IS - 13

ER -

PARP-1 regulates expression of TGF-β receptors in T cells.

Abstract

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