Transforming Growth Factor-β Suppresses the Ability of Ski to Inhibit Tumor Metastasis by Inducing Its Degradation

Scolan, Erwan Le; Zhu, Qiangqiang; Wang, Long; Bandyopadhyay, Abhik; Javelaud, Delphine; Mauviel, Alain; Sun, LuZhe; Luo, Kunxin

doi:10.1158/0008-5472.can-07-6793

Cited by 94 publications

(109 citation statements)

References 47 publications

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“…Examples of such Smad repressors are Ski and SnoN, as described in the previous section. According to the current model, Ski and SnoN seem to play dual roles in cancer progression, despite the fact that previous knowledge favored an oncogenic role for these proteins [88,[105][106][107]. The oncogenic potential of Ski and SnoN is known to be mediated by their ability to bind directly to nuclear Smad complexes and repress their transcriptional activities [85,[108][109][110][111].…”

Section: Relevance Of Stability Regulation Of Tgfβ Pathway Componentsmentioning

confidence: 74%

“…Whether ectodermin/ TIF1γ can also reach alternative substrates via its interaction with Smad4 and phosphorylated Smad2 remains an interesting open question [82]. The best understood targets of R-Smad-mediated ubiquitination are the nuclear co-repressors Ski and SnoN, which bind to chromatin via their interaction with Smad4 and phosphorylated R-Smads [50,[83][84][85][86][87][88]. The current prevailing model favors a chromatin-tethered Ski/SnoN/ Smad4 complex that represses specific target genes of TGFb signaling (Figure 3).…”

Section: Regulation Of Stability Of I-smads and Other Signaling Targetsmentioning

confidence: 99%

“…The current prevailing model favors a chromatin-tethered Ski/SnoN/ Smad4 complex that represses specific target genes of TGFb signaling (Figure 3). After phosphorylation by receptors, R-Smads enter the nucleus; they associate with Ub ligases such as the anaphase promoting complex (APC, which is best known for regulation of cell cycle progression), Smurf2 or Arkadia, and the concerted action of these Ub ligases leads to ubiquitination and proteasomal degradation of Ski or SnoN [50,83,84,[86][87][88]. This leaves the target chromatin locus free from the repressors and allows the incoming R-Smads to establish positive regulation of RNA polymerase II and mRNA synthesis.…”

Section: Regulation Of Stability Of I-smads and Other Signaling Targetsmentioning

confidence: 99%

“…The oncogenic potential of Ski and SnoN is known to be mediated by their ability to bind directly to nuclear Smad complexes and repress their transcriptional activities [85,[108][109][110][111]. Thus, when the synergistic activities of the APC, Smurf2 and Arkadia Ub ligases lead to poly-ubiquitination and degradation of Ski and SnoN, the tumor suppressor action of the TGFb/ Smad pathway is enhanced [50,83,84,[86][87][88]. But Smurf2 and Arkadia can also target Smad2 and Smad4 for degradation, thus removing two central components of the tumor suppressor pathway of TGFb [41,42,54,61].…”

Section: Relevance Of Stability Regulation Of Tgfβ Pathway Componentsmentioning

confidence: 99%

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Regulating the stability of TGFβ receptors and Smads

et al. 2008

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Abbreviations: AIP4 (atrophin 1-interacting protein 4); BMP (bone morphogenetic protein); CHIP (carboxyl terminus of Hsc70-interacting protein); GSK3b (glycogen synthase kinase 3-b); HECT (homologous to E6-AP carboxyl terminus); MAPK (mitogen-activated protein kinase); NEDD4-2 (neural precursor cell expressed, developmentally downregulated 4-2); PIAS (protein inhibitor of activated Stat); Smurf (Smad ubiquitylation regulatory factor); STRAP (serine-threonine kinase receptorassociated protein); SUMO (small ubiquitin-like modifier); TbRI/TbRII (TGFb receptor type I and II); TGFb (transforming growth factor b); WWP1 (WW domain-containing protein 1); Ub (ubiquitin) npg Transforming growth factor β (TGFβ) controls cellular behavior in embryonic and adult tissues. TGFβ binding to serine/threonine kinase receptors on the plasma membrane activates Smad molecules and additional signaling proteins that together regulate gene expression. In this review, mechanisms and models that aim at explaining the coordination between several components of the signaling network downstream of TGFβ are presented. We discuss how the activity and duration of TGFβ receptor/Smad signaling can be regulated by post-translational modifications that affect the stability of key proteins in the pathway. We highlight links between these mechanisms and human diseases, such as tissue fibrosis and cancer. Regulating the stability of TGFβ receptors and Smads

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Section: Relevance Of Stability Regulation Of Tgfβ Pathway Componentsmentioning

confidence: 74%

Section: Regulation Of Stability Of I-smads and Other Signaling Targetsmentioning

confidence: 99%

Section: Regulation Of Stability Of I-smads and Other Signaling Targetsmentioning

confidence: 99%

Section: Relevance Of Stability Regulation Of Tgfβ Pathway Componentsmentioning

confidence: 99%

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Regulating the stability of TGFβ receptors and Smads

et al. 2008

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“…Consequent to the initial decrease of SnoN, TGF-β induces the production of SnoN to the steady state level. In some cell types, TGF-β also induces degradation of Ski [221]. In addition, SnoN and Ski modify the TGF-β signaling cascade by regulating Smad7 production.…”

Section: Crosstalk With Tgf-β Signalingmentioning

confidence: 99%

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

Zhou

Qiao

Shetty

et al. 2013

Cell. Mol. Life Sci.

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Estrogen and estrogen receptors (ERs) are critical regulators of breast epithelial cell proliferation, differentiation, and apoptosis. Compromised signaling vis-à-vis the estrogen receptor is believed © Springer Basel 2013 yow4@pitt.edu. ), which predicts for response to endocrine-based therapy; however, innate or acquired resistance to endocrinebased drugs remains a serious challenge. The complexity of regulation for estrogen signaling coupled with the crosstalk of other oncogenic signaling pathways is a reason for endocrine therapy resistance. Alternative strategies that target novel molecular mechanisms are necessary to overcome this current and urgent gap in therapy. A thorough analysis of estrogen-signaling regulation is critical. In this review article, we will summarize current insights into the regulation of estrogen signaling as related to breast carcinogenesis and breast cancer therapy. NIH Public Access

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The Ski Protein is Involved in the Transformation Pathway of Aurora Kinase A

et al. 2015

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Oncogenic kinase Aurora A (AURKA) has been found to be overexpresed in several tumors including colorectal, breast, and hematological cancers. Overexpression of AURKA induces centrosome amplification and aneuploidy and it is related with cancer progression and poor prognosis. Here we show that AURKA phosphorylates in vitro the transcripcional co-repressor Ski on aminoacids Ser326 and Ser383. Phosphorylations on these aminoacids decreased Ski protein half-life. Reduced levels of Ski resulted in centrosomes amplification and multipolar spindles formation, same as AURKA overexpressing cells. Importantly, overexpression of Ski wild type, but not S326D and S383D mutants inhibited centrosome amplification and cellular transformation induced by AURKA. Altogether, these results suggest that the Ski protein is a target in the transformation pathway mediated by the AURKA oncogene.

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Transforming Growth Factor-β Suppresses the Ability of Ski to Inhibit Tumor Metastasis by Inducing Its Degradation

Abstract: c-Ski is an important corepressor of transforming

Cited by 94 publications

References 47 publications

Regulating the stability of TGFβ receptors and Smads

Regulating the stability of TGFβ receptors and Smads

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

The Ski Protein is Involved in the Transformation Pathway of Aurora Kinase A

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