Tbx3 impinges on the p53 pathway to suppress apoptosis, facilitate cell transformation and block myogenic differentiation

Carlson, Hanqian L.; Ota, Sara; Song, Youngsup; Chen, Yanwen; Hurlin, Peter J.

doi:10.1038/sj.onc.1205476

Cited by 89 publications

(89 citation statements)

References 35 publications

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“…Thus, Myc must work through the agency of other transcription factors or signaling proteins that regulate Arf transcription. Indeed some likely culprits have been identified, including the transcription factors Bmi-1, Twist, Tbx2 and Tbx3, all of which repress Arf transcription and block Mycinduced apoptosis (Jacobs et al, 1999a(Jacobs et al, , 2000Maestro et al, 1999;Brummelkamp et al, 2002;Carlson et al, 2002;Lingbeek et al, 2002). Furthermore, reductions in Bmi-1 impair Myc-induced tumorigenesis through augmenting an Arf-dependent apoptotic response (Jacobs et al, 1999a).…”

Section: Myc Triggers the Arf-p53 Tumor Suppressor Pathwaymentioning

confidence: 99%

Myc pathways provoking cell suicide and cancer

2003

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Section: Myc Triggers the Arf-p53 Tumor Suppressor Pathwaymentioning

confidence: 99%

Myc pathways provoking cell suicide and cancer

2003

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“…Tbx3 is required for normal breast development (13), with mutations in the Tbx3 gene linked to ulnar-mammary syndrome (14). Moreover, Tbx3 can cooperate with Ras and Myc to induce cellular transformation and suppress apoptosis (15). Importantly, both Tbx3 and the highly related factor Tbx2 are transcriptional repressors (16 -19) and can suppress senescence through a mechanism involving repression of the expression of the p19 ARF (p14) gene (20 -22).…”

Section: Introductionmentioning

confidence: 99%

Tbx2 Directly Represses the Expression of the p21WAF1 Cyclin-Dependent Kinase Inhibitor

et al. 2004

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T-box factors play a crucial role in the development of many tissues, and mutations in T-box factor genes have been implicated in multiple human disorders. Some T-box factors have been implicated in cancer; for example, Tbx2 and Tbx3 can suppress replicative senescence, whereas Tbx3 can cooperate with Myc and Ras in cellular transformation. The p21 WAF1 cyclin-dependent kinase inhibitor plays a key role in senescence and in cell cycle arrest after DNA damage. Here, using a combination of in vitro DNA-binding, transfection, and chromatin immunoprecipitation assays, we show that Tbx2 can bind and repress the p21 promoter in vitro and in vivo. Moreover, small interfering RNA-mediated down-regulation of Tbx2 expression results in a robust activation of p21 expression. Taken together, these results implicate Tbx2 as a novel direct regulator of p21 expression and have implications for our understanding of the role of T-box factors in the regulation of senescence and oncogenesis, as well as in development.

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“…Both Tbx2 and Tbx3, for example, can prevent senescence in mouse embryonic fibroblasts and ST.Hdh Q111 striatal cells through a mechanism involving their ability to repress the cyclin-dependent kinase inhibitors p19 ARF (Jacobs et al, 2000;Carlson et al, 2001;Brummelkamp et al, 2002) and p21 WAF1/CIP1/SDII (referred to as p21) (Prince et al, 2004). Ectopic expression of Tbx3 together with oncogenic Ras or Myc in embryonic mouse fibroblasts leads to cellular transformation and suppression of apoptosis (Carlson et al, 2002). Furthermore, both Tbx2 and Tbx3 are expressed in the developing breast (Jerome-Majewska et al, 2005) and their genes are amplified and/or overexpressed in some breast tumors (Sinclair et al, 2002;Packham and Brook, 2003) and in certain breast cancer cell lines Fan et al, 2004).…”

Section: Introductionmentioning

confidence: 99%