PARP-1 Attenuates Smad-Mediated Transcription

被引：112
作者：
Lonn, Peter [1 ]
van der Heide, Lars P. [1 ]
Dahl, Markus [1 ]
Hellman, Ulf [1 ]
Heldin, Carl-Henrik [1 ]
Moustakas, Aristidis [1 ]
机构：
[1] Uppsala Univ, Ludwig Inst Canc Res, SE-75124 Uppsala, Sweden
来源：
MOLECULAR CELL | 2010年 / 40卷 / 04期
基金：
瑞典研究理事会;
关键词：
GROWTH-FACTOR-BETA; DNA-BINDING; MH1; DOMAIN; POLY(ADP-RIBOSE); SEQUENCE;
D O I：
10.1016/j.molcel.2010.10.029
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The versatile cytokine transforming growth factor beta (TGF-beta) regulates cellular growth, differentiation, and migration during embryonic development and adult tissue homeostasis. Activation of TGF-beta receptors leads to phosphorylation of Smad2 and Smad3, which oligomerize with Smad4 and accumulate in the nucleus where they recognize gene regulatory regions and orchestrate transcription. Termination of Smad-activated transcription involves Smad dephosphorylation, nuclear export, or ubiquitin-mediated degradation. In an unbiased proteomic screen, we identified poly(ADP-ribose) polymerase-1 (PARP-1) as a Smad-interacting partner. PARP-1 dissociates Smad complexes from DNA by ADP-ribosylating Smad3 and Smad4, which attenuates Smad-specific gene responses and TGF-beta-induced epithelial-mesenchymal transition. Thus, our results identify ADP-ribosylation of Smad proteins by PARP-1 as a key step in controlling the strength and duration of Smad-mediated transcription.
引用
收藏
页码：521 / 532
页数：12
相关论文
共 27 条
  • [1] DNA-independent PARP-1 activation by phosphorylated ERK2 increases EIk1 activity: A link to histone acetylation
    Cohen-Armon, Malka
    Visochek, Leonid
    Rozensal, Dana
    Kalal, Adi
    Geistrikh, Ilona
    Klein, Rodika
    Bendetz-Nezer, Sarit
    Yao, Zhong
    Seger, Rony
    [J]. MOLECULAR CELL, 2007, 25 (02) : 297 - 308
  • [2] The tumor suppressor Smad4 is required for transforming growth factor β-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells
    Deckers, M
    van Dinther, M
    Buijs, J
    Que, N
    Löwik, C
    van der Pluijm, G
    ten Dijke, P
    [J]. CANCER RESEARCH, 2006, 66 (04) : 2202 - 2209
  • [3] Direct binding of Smad3 and Smad4 to critical TGFβ-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene
    Dennler, S
    Itoh, S
    Vivien, D
    ten Dijke, P
    Huet, S
    Gauthier, JM
    [J]. EMBO JOURNAL, 1998, 17 (11) : 3091 - 3100
  • [4] A short amino-acid sequence in MH1 domain is responsible for functional differences between Smad2 and Smad3
    Dennler, S
    Huet, S
    Gauthier, JM
    [J]. ONCOGENE, 1999, 18 (08) : 1643 - 1648
  • [5] Specificity and versatility in TGF-β signaling through Smads
    Feng, XH
    Derynck, R
    [J]. ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2005, 21 : 659 - 693
  • [6] CCCTC-binding factor activates PARP-1 affecting DNA methylation machinery
    Guastafierro, Tiziana
    Cecchinelli, Barbara
    Zampieri, Michele
    Reale, Anna
    Riggio, Giuseppe
    Sthandier, Olga
    Zupi, Gabriella
    Calabrese, Lilia
    Caiafa, Paola
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (32) : 21873 - 21880
  • [7] The enzymatic and DNA binding activity of PARP-1 are not required for NF-κB coactivator function
    Hassa, PO
    Covic, M
    Hasan, S
    Imhof, R
    Hottiger, MO
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (49) : 45588 - 45597
  • [8] Nucleocytoplasmic shuttling of Smad proteins
    Hill, Caroline S.
    [J]. CELL RESEARCH, 2009, 19 (01) : 36 - 46
  • [9] Synergism between transcription factors TFE3 and Smad3 in transforming growth factor-β-induced transcription of the Smad7 gene
    Hua, XX
    Miller, ZA
    Benchabane, H
    Wrana, JL
    Lodish, HF
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (43) : 33205 - 33208
  • [10] Poly(ADP-ribosyl)ation by PARP-1:: 'PAR-laying' NAD+ into a nuclear signal
    Kim, MY
    Zhang, T
    Kraus, WL
    [J]. GENES & DEVELOPMENT, 2005, 19 (17) : 1951 - 1967
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