Isolation of human cDNA clones of<i>ski</i>and the ski-related gene,<i>sno</i>

Nomura, Nobuo; Sasamoto, Shigemi; Ishii, Shunsuke; Date, Taro; Matsui, Minami; Ishizaki, Ryotaro

doi:10.1093/nar/17.14.5489

Cited by 167 publications

(216 citation statements)

References 45 publications

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“…Overexpression of c-Ski abolished TGF-␤-induced growth inhibition (Luo et al, 1999;Sun et al, 1999;Xu et al, 2000). High levels of expression of c-Ski were reported in several tumor cell lines (Nomura et al, 1989;Fumagalli et al, 1993) and in melanomas in vivo (Reed et al, 2001). Inhibition of TGF-␤ signaling is thus regarded as a part of the mechanism of oncogenesis by Ski proteins (He et al, 2003).…”

Section: Introductionmentioning

confidence: 98%

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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Section: Introductionmentioning

confidence: 98%

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

Takeda

Mizuide

Oka³

et al. 2004

MBoC

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“…High levels of Ski or SnoN are associated with many types of human cancer cells. 7,8 Ski or SnoN antagonize TGF-b signaling through direct interaction with Smad4, Smad2 or Smad3. [9][10][11][12] A 8-bp palindromic sequence (GTCTAGAC) was initially identified to be a high-affinity binding site for Ski.…”

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confidence: 99%

Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues

Arndt

Poser

Schubert

et al. 2005

Laboratory Investigation

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The Sloan Kettering Virus (Ski) family of nuclear oncoproteins represses transforming growth factor-b (TGF-b) signaling through inhibition of transcriptional activity of Smad proteins. Here, we report the discovery of a new functional Smad suppressing element on chromosome 18 (Fussel-18). Fussel-18 encodes for a protein of 297 amino acids sharing characteristic structural features, significant homology and similar genomic organization with the homolog Ski family members, Ski and Ski-related novel sequence (Sno). In contrast to Ski and Sno, which are ubiquitously expressed in human tissues, in situ hybridization, RT-PCR, Western blot and immunohistochemistry revealed a highly specific expression pattern for Fussel-18 in neuronal tissues, especially in the cerebellum, the spinal cord and dorsal root ganglia, during both embryogenesis and adult stage. Functionally, we determined interaction of Fussel-18 with Smad 2 and Smad 3 together with an inhibitory activity on TGF-b signaling. Fussel-18 is the first example of a Smad-binding protein with a highly restricted expression pattern within the nervous system.

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“…Previous reports have demonstrated that ski is ubiquitously expressed at low levels (Colmenares and Stavnezer, 1990;Nomura et al, 1989). Reverse transcriptase PCR analysis detected skip expression in all cell lines that were tested (data not shown).…”

Section: Discussionmentioning

confidence: 62%

“…V-Ski is truncated at the amino and carboxyl termini compared to the cellular proto-oncogene c-Ski. Ski has been cloned from several species including human, chicken, and Xenopus (Nomura et al, 1989;Sleeman and Laskey, 1993;Sutrave et al, 1990a); and is the founding member of a family of proteins which includes itself and the Ski related protein Sno (Boyer et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…Quail embryo ®broblasts infected with a retrovirus expressing Ski di erentiate into myoblasts capable of forming myotubes in culture (Colmenares and Stavnezer, 1989), and transgenic mice overexpressing a truncated c-Ski protein display enlarged skeletal muscle mass compared to their normal litter mates (Sutrave et al, 1990b). Despite evidence for a role in muscle development, c-Ski is only expressed at very low levels in normal skeletal muscle tissue, similar to its expression levels detected in other adult tissues (Colmenares and Stavnezer, 1990;Nomura et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

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