Smad7 inhibits the survival nuclear factor κB and potentiates apoptosis in epithelial cells

Lallemand, François; Mazars, Anne; Prunier, Céline; Bertrand, F; Kornprost, Michel; Gallea, Sylvie; Roman-Roman, Sergio; Cherqui, Gisèle; Atfi, Azeddine

doi:10.1038/sj.onc.1204167

Cited by 107 publications

(84 citation statements)

References 25 publications

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“…The expression of Smad7 can also be induced by interferon-␥ and by TNF-␣, raising the interesting possibility that Smad7 may fulfill other cellular functions independent of its inhibitory role (13,14). Consistent with this, overexpression of Smad7 has been reported to sensitize various cell types to many forms of cell death (15,16). However, the mechanism by which Smad7 induces cell death remains largely undefined.…”

mentioning

confidence: 52%

Evidence for a Role of the JNK Cascade in Smad7-mediated Apoptosis

Mazars

Lallemand

Prunier

et al. 2001

Journal of Biological Chemistry

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mentioning

confidence: 52%

Evidence for a Role of the JNK Cascade in Smad7-mediated Apoptosis

Mazars

Lallemand

Prunier

et al. 2001

Journal of Biological Chemistry

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“…Smad7 may also recruit other transcriptional cofactors to caspase 8 promoter. 5 Another inhibitory Smad protein, Smad6, recruits the transcription corepressor C-terminal binding protein to repress bone morphogenetic protein-induced Id1 transcription (44). Smad6 also interacts with homeobox c-8 as a transcriptional corepressor to inhibit Smad1-induced transcriptional activation (45).…”

Section: Discussionmentioning

confidence: 99%

“…Smad7 sensitizes tumor cells to tumor necrosis factor-␣ (TNF-␣) and other death signals by modulating the NF-B survival pathway (3)(4)(5). Also, overexpression of Smad7 in melanoma and mammary carcinoma cells can impair tumor growth and bone metastasis (6,7).…”

mentioning

confidence: 99%

Smad7 Protein Induces Interferon Regulatory Factor 1-dependent Transcriptional Activation of Caspase 8 to Restore Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-mediated Apoptosis

Kim

et al. 2013

Journal of Biological Chemistry

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Background: Smad7 may have biological roles other than inhibition of TGF-␤ signaling. Results: Smad7 activates caspase 8 expression by recruiting IRF1, thereby inducing TRAIL-mediated apoptosis. Conclusion: Smad7 functions as a transcriptional coactivator of IRF1 to regulate the expression of target genes. Significance: Smad7-inducing reagents can be used as anti-cancer drugs for tumors that have defects in caspase 8 expression.

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“…The involvement of the Smad pathway in TGF-b-induced apoptosis through XIAP, ARTS, or Daxx is unclear. Interestingly, there are several reports that Smad7, a downstream target gene of TGF-b family members, can ef®ciently induces apoptosis in epithelial cells (Landstro Èm et al, 2000;Lallemand et al, 2001;Mazars et al, 2001;Schiffer et al, 2001) independent of its antagonistic effect on TGFb/Smad signaling ). Smad7 may induce apoptosis by inhibiting the survival NFkB or by activation of JNK .…”

Section: Regulation Of Apoptosis By Smadsmentioning

confidence: 99%

Regulation of cell proliferation by Smad proteins

Dijke

Goumans

Itoh

2002

Journal Cellular Physiology

399

278

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Transforming growth factor-b (TGF-b) family members which include TGF-bs, activins, and bone morphogenetic proteins (BMPs) regulate a broad spectrum of biological responses on a large variety of cell types. TGF-b family members initiate their cellular responses by binding to distinct receptors with intrinsic serine/ threonine kinase activity and activation of speci®c downstream intracellular effectors termed Smad proteins. Smads relay the signal from the cell membrane to the nucleus, where they affect the transcription of target genes. Smad activation, subcellular distribution, and stability have been found to be intricately regulated and a broad array of transcription factors have been identi®ed as Smad partners. Important activities of TGF-b are its potent anti-mitogenic and pro-apoptotic effects that, at least in part, are mediated via Smad proteins. Escape from TGF-b/ Smad-induced growth inhibition and apoptosis is frequently observed in tumors. Certain Smads have been found to be mutated in speci®c types of cancer and gene ablation of particular Smads in mice has revealed increased rate of tumorigenesis. In late stage tumors, TGF-b has been shown to function as a tumor promoter. TGFb can stimulate the de-differentiation of epithelial cells to malignant invasive and metastatic ®broblastic cells. Interestingly, TGF-b may mediate these effects directly on tumor cells via subverted Smad-dependent and/or Smad-independent pathways.

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Smad7 inhibits the survival nuclear factor κB and potentiates apoptosis in epithelial cells

Cited by 107 publications

References 25 publications

Evidence for a Role of the JNK Cascade in Smad7-mediated Apoptosis

Evidence for a Role of the JNK Cascade in Smad7-mediated Apoptosis

Smad7 Protein Induces Interferon Regulatory Factor 1-dependent Transcriptional Activation of Caspase 8 to Restore Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-mediated Apoptosis

Regulation of cell proliferation by Smad proteins

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