Ski/Sno and TGF-β signaling

Liu, Xuedong; Sun, Yin; Weinberg, Robert A.; Lodish, Harvey F.

doi:10.1016/s1359-6101(00)00031-9

Cited by 180 publications

(162 citation statements)

References 59 publications

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“…This results in their release from the receptor, heterodimerization with the signal mediator Smad4 and subsequent translocation into the nucleus (Liu et al, 1997). Here receptor-activated Smads and Smad4 form complexes with potential co-regulators of transcription such as CBP/p300 (Feng et al, 1998), FAST-1 (Chen et al, 1997) and SKI/SNO (Liu et al, 2001b). The composition of these transcriptional complexes is believed to be largely responsible for the celltype-specific effects of TGFb.…”

Section: Transforming Growth Factor B Signaling Axismentioning

confidence: 99%

Dysregulation of growth factor signaling in human hepatocellular carcinoma

2006

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Section: Transforming Growth Factor B Signaling Axismentioning

confidence: 99%

Dysregulation of growth factor signaling in human hepatocellular carcinoma

2006

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“…Two such kinds of antagonists are C-Ski and SnoN, two structurally related TGF-␤ antagonists (Stroschein et al, 1999;Wu et al, 2002). Similar to TGIF, C-Ski and SnoN proteins suppress TGF-␤ signaling by interacting with Smad proteins, recruiting histone deacetylase complex and competing out transcriptional activators (reviewed by Liu et al, 2001). Both C-Ski and SnoN have been reported to be expressed in the murine central nervous system (Lyons et al, 1994;Pelzer et al, 1996).…”

Section: Tgif ؊/؊ Embryos Show Normal Brain and Spinal Cord Patterningmentioning

confidence: 99%

Expression and functional analysis of Tgif during mouse midline development

Jin

McKinney

et al. 2005

Developmental Dynamics

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“…In contrast, transcriptional corepressors, including TGIF, c-Ski, and SnoN, physically interact with Smads, and repress TGF-␤ signaling through recruitment of histone deacetylases (HDACs) (Massagué and Chen, 2000;Liu et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Interaction with Smad4 Is Indispensable for Suppression of BMP Signaling by c-Ski

Takeda

Mizuide

Oka³

et al. 2004

MBoC

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c-Ski is a transcriptional corepressor that interacts strongly with Smad2, Smad3, and Smad4 but only weakly with Smad1 and Smad5. Through binding to Smad proteins, c-Ski suppresses signaling of transforming growth factor-␤ (TGF-␤) as well as bone morphogenetic proteins (BMPs). In the present study, we found that a mutant of c-Ski, termed c-Ski (ARPG) inhibited TGF-␤/activin signaling but not BMP signaling. Selectivity was confirmed in luciferase reporter assays and by determination of cellular responses in mammalian cells (BMP-induced osteoblastic differentiation of C2C12 cells and TGF-␤-induced epithelial-to-mesenchymal transdifferentiation of NMuMG cells) and Xenopus embryos. The ARPG mutant recruited histone deacetylases 1 (HDAC1) to the Smad3-Smad4 complex but not to the Smad1/5-Smad4 complex. c-Ski (ARPG) was unable to interact with Smad4, and the selective loss of suppression of BMP signaling by c-Ski (ARPG) was attributed to the lack of Smad4 binding. We also found that c-Ski interacted with Smad3 or Smad4 without disrupting Smad3-Smad4 heteromer formation. c-Ski (ARPG) would be useful for selectively suppressing TGF-␤/activin signaling. INTRODUCTIONCytokines of the transforming growth factor-␤ (TGF-␤) superfamily are multifunctional proteins that regulate growth, differentiation, apoptosis, and morphogenesis of a wide variety of cell types. TGF-␤ and related factors bind to two different types of serine/threonine kinase receptors, termed type I and type II (Derynck et al., 1998;Attisano and Wrana, 2000;Shi and Massagué, 2003). Type I receptor is activated by type II receptor upon ligand binding and transduces signals into cytoplasm through phosphorylation of receptorregulated Smads (R-Smads). Phosphorylated R-Smads interact with Co-Smad (Smad4) and translocate into the nucleus. Nuclear Smad complexes regulate transcription of target genes in cooperation with transcriptional activators/repressors as well as with coactivators/corepressors . Of the eight different mammalian Smad proteins, Smad1, Smad5, and Smad8 are R-Smads activated by BMP family members, whereas Smad2 and Smad3 are R-Smads activated by TGF-␤ and activin.Transcription of target genes by TGF-␤ is upregulated by binding of Smads to transcriptional coactivators, including p300 and CBP, which induce acetylation of histones and loosen chromatin structure (Massagué and Chen, 2000;Miyazono et al., 2001). In contrast, transcriptional corepressors, including TGIF, c-Ski, and SnoN, physically interact with Smads, and repress TGF-␤ signaling through recruitment of histone deacetylases (HDACs) (Massagué and Chen, 2000;Liu et al., 2001).c-Ski was originally identified as a cellular counterpart of a retroviral oncogene product, v-Ski (Li et al., 1986). c-Ski physically interacts with Smad2, Smad3, and Smad4, thus antagonizing signal transduction in the TGF-␤ pathway (Akiyoshi et al., 1999;Luo et al., 1999;Sun et al., 1999;Xu et al., 2000). Overexpression of c-Ski abolished TGF-␤-induced growth inhibition (Luo et al., 1999;Sun et al., 1999;Xu et al., 200...

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Ski/Sno and TGF-β signaling

Cited by 180 publications

References 59 publications

Dysregulation of growth factor signaling in human hepatocellular carcinoma

Dysregulation of growth factor signaling in human hepatocellular carcinoma

Expression and functional analysis of Tgif during mouse midline development

Interaction with Smad4 Is Indispensable for Suppression of BMP Signaling by c-Ski

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