TGFβ1-Induced Activation of ATM and p53 Mediates Apoptosis in a Smad7-Dependent Manner

Zhang, Shouting; Ekman, Martin; Thakur, Noopur; Bu, Shizhong; Davoodpour, Padideh; Grimsby, Susanne; Tagami, Seicchi; Heldin, Carl‐Henrik; Landström, Maréne

doi:10.4161/cc.5.23.3523

Cited by 54 publications

(33 citation statements)

References 42 publications

(53 reference statements)

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“…Recent studies have shown that substrates of Arkadia, Smad7 and SnoN/c-Ski, appear to have Smad-independent functions. Smad7 has been shown to regulate various non-Smad signaling pathways (56). Smad7 and c-Ski have been reported to enhance myogenic differentiation through acting on MyoD (51,57).…”

Section: Discussionmentioning

confidence: 99%

Arkadia Induces Degradation of SnoN and c-Ski to Enhance Transforming Growth Factor-β Signaling

Nagano

Mavrakis

Lee

et al. 2007

Journal of Biological Chemistry

151

140

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Section: Discussionmentioning

confidence: 99%

Arkadia Induces Degradation of SnoN and c-Ski to Enhance Transforming Growth Factor-β Signaling

Nagano

Mavrakis

Lee

et al. 2007

Journal of Biological Chemistry

151

140

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show abstract

“…27,36,37 For example, Smad2/3 and p53 have been shown to physically interact and jointly regulate the transcription of several TGF-␤ target genes. 38 Experiments also suggest that p53 activation conveys cues from extracellular signals within the TGF-␤ gene expression program and support the idea that p53 acts as an integration node between Ras/mitogen-activated protein kinase and TGF-␤ pathways.…”

Section: Discussionmentioning

confidence: 99%

Lack of Fetuin-A (α2-HS-Glycoprotein) Reduces Mammary Tumor Incidence and Prolongs Tumor Latency via the Transforming Growth Factor-β Signaling Pathway in a Mouse Model of Breast Cancer

Guillory

Sakwe

Saria

et al. 2010

The American Journal of Pathology

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The present analyses were done to define the role of fetuin-A (Fet) in mammary tumorigenesis using the polyoma middle T antigen (PyMT) transgenic mouse model. We crossed Fet-null mice in the C57BL/6 background with PyMT mice in the same background and after a controlled breeding protocol obtained PyMT/Fet ؉/؉ , PyMT/Fet ؉/؊ , and PyMT/Fet ؊/؊ mice that were placed in control and experimental groups.

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“…Our research (33,34), and that of others (35)(36)(37), has shown that TGFh signaling plays an essential role in p53 activity and DNA damage-induced apoptosis. Because TGFh inhibition can compromise p53 phosphorylation that mediates its activity (33,34), and loss of p53 can also increase CA, tetraploidy, and tumorigenesis (22, 38), we considered whether TGFh was acting via p53.…”

Section: Cancer Researchmentioning

confidence: 99%

Targeted and Nontargeted Effects of Ionizing Radiation That Impact Genomic Instability

et al. 2008

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Radiation-induced genomic instability, in which the progeny of irradiated cells display a high frequency of nonclonal genomic damage, occurs at a frequency inconsistent with mutation. We investigated the mechanism of this nontargeted effect in human mammary epithelial cells (HMEC) exposed to low doses of radiation. We identified a centrosome-associated expression signature in irradiated HMEC and show here that centrosome deregulation occurs in the first cell cycle after irradiation, is dose dependent, and that viable daughters of these cells are genomically unstable as evidenced by spontaneous DNA damage, tetraploidy, and aneuploidy. Clonal analysis of genomic instability showed a threshold of >10 cGy. Treatment with transforming growth factor B1 (TGFB), which is implicated in regulation of genomic stability and is activated by radiation, reduced both the centrosome expression signature and centrosome aberrations in irradiated HMEC. Furthermore, TGFB inhibition significantly increased centrosome aberration frequency, tetraploidy, and aneuploidy in nonirradiated HMEC. Rather than preventing radiation-induced or spontaneous centrosome aberrations, TGFB selectively deleted unstable cells via p53-dependent apoptosis. Together, these studies show that radiation deregulates centrosome stability, which underlies genomic instability in normal human epithelial cells, and that this can be opposed by radiation-induced TGFB signaling.

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TGFβ1-Induced Activation of ATM and p53 Mediates Apoptosis in a Smad7-Dependent Manner

Cited by 54 publications

References 42 publications

Arkadia Induces Degradation of SnoN and c-Ski to Enhance Transforming Growth Factor-β Signaling

Arkadia Induces Degradation of SnoN and c-Ski to Enhance Transforming Growth Factor-β Signaling

Lack of Fetuin-A (α2-HS-Glycoprotein) Reduces Mammary Tumor Incidence and Prolongs Tumor Latency via the Transforming Growth Factor-β Signaling Pathway in a Mouse Model of Breast Cancer

Targeted and Nontargeted Effects of Ionizing Radiation That Impact Genomic Instability

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