Regulation of PTEN Transcription by p53

Stambolic, Vuk; MacPherson, David; Sas, Daryl F.; Lin, Yunping; Snow, Brian J.; Jang, Yingju; Benchimol, Samuel; Mak, Tak W.

doi:10.1016/s1097-2765(01)00323-9

Cited by 828 publications

(687 citation statements)

References 29 publications

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“…Because PTEN can be transactivated by p53 (Stambolic et al, 2001), and we previously found Figure 2a, both p53 and PTEN protein levels were reduced by Id-1 and these changes were restored by suppression of Id-1 using retroviral antisense construct (left). These mRNA levels were also downregulated by Id-1, suggesting that Id-1 regulated both p53 and PTEN at the transcriptional level ( Figure 2b).…”

Section: Id-1 Inhibits Pten Transcription Through P53 Downregulationmentioning

confidence: 71%

“…C-Jun binds to the AP-1 site of the PTEN promoter and can suppress its transcription, whereas Egr-1 activates PTEN transcription by direct binding to the PTEN 5 0 untranslated region (Virolle et al, 2001). In addition, p53 has been reported as a crucial PTEN transactivator (Stambolic et al, 2001). It was also reported that suppression of p53 mutant expression is involved in upregulation of p21 and PTEN (Vikhanskaya et al, 2007).…”

Section: Discussionmentioning

confidence: 96%

“…In addition, several studies have shown that PTEN is linked to p53, another crucial tumor suppressor gene. It has been shown that PTEN transcription can be regulated by p53 because the PTEN promoter contains a p53-binding site element that is required for transactivation of PTEN (Stambolic et al, 2001). Loss of p53 resulted in reduction of PTEN expression and increased ultraviolet-induced Akt activation in mouse epidermal CI41 cells (Wang et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

et al. 2008

Oncogene

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Inhibitor of differentiation-1 (Id-1) has been accepted as a putative oncogene to promote oncogenic processes through inactivation of tumor suppressors and activation of growth promoting pathways. Here, we show that Id-1 activates the Akt pathway by inhibition of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) transcription through downregulation of p53. Id-1 negatively regulated both p53 and PTEN at the transcriptional level. In promoter assay with serial deletion and chromatin immunoprecipitation assay, the binding of p53 to the PTEN promoter was reduced by Id-1, suggesting that Id-1 regulates PTEN transcription through its p53 modulation. This led to Akt phosphorylation at Ser473 and the activation of the Akt-mediated canonical Wnt signaling pathway. The glycogen synthase kinase-3b phosphorylation at Ser9, stabilization and nuclear localization of b-catenin, T-cell factor (TCF)/lymphoid enhancer factor transactivation activity and cyclin D1 expression were enhanced by Id-1. On the other hand, Akt-mediated p27 Kip1 phosphorylation at Thr157 and its cytosolic localization were also increased in Id-1 overexpressing MCF7 cells. In conclusion, our results disclose Id-1 as a novel PTEN inhibitor that could activate the Akt pathway and its downstream effectors, the Wnt/TCF pathway and p27 Kip1 phosphorylation and suggest that the oncogenic function of Id-1 may be partly attributed to its PTEN inhibition in human breast carcinogenesis.

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Section: Id-1 Inhibits Pten Transcription Through P53 Downregulationmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

et al. 2008

Oncogene

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“…Suppression of the IGF-1 receptor is accompanied by reduced IGF-1R and IRS-1 (a downstream modulator of IGF-1R signaling) tyrosine phosphorylation (Ohlsson et al, 1998). P53 also upregulates PTEN transcription, a tumor suppressor and lipid/tyrosine phosphatase that inhibits phosphatidylinositol 3-kinase (PI3K) function downstream of IGF-1 (Figure 1) (Stambolic et al, 2001). Finally, p53 also directly suppresses PI3K function by inhibiting p110 alpha, a subunit of the PI3K complex .…”

Section: How Does the Dna Damage Response Suppress Igf-1 Signaling?mentioning

confidence: 99%

How does suppression of IGF-1 signaling by DNA damage affect aging and longevity?

Hinkal

Donehower

2008

Mechanisms of Ageing and Development

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Long-lived animals have evolved a robust set of defenses to maintain genomic integrity over their entire lifespan. The DNA damage response and DNA repair pathways are critical pillars of organismal defenses, minimizing somatic mutations in both post-mitotic and mitotic cells. These genomic maintenance systems not only prevent the premature emergence of cancers, but may also maintain normal tissue function and organismal longevity. Genetic defects in a number of DNA repair and DNA damage response genes often leads to a dramatic increase in cancer incidence; in other cases, premature aging or progeroid syndromes may be induced. In this review, we discuss two recent reports of two nucleotide excision repair deficient models that exhibit dramatic premature aging and shortened longevity. The DNA repair defects were also associated with a significant inhibition of the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis, an endocrine signaling pathway shown to influence aging and longevity in both vertebrates and invertebrates. Potential mechanisms of how DNA damage might affect IGF-1 signaling and aging are discussed, with a particular emphasis on the role of such signaling alterations in the adult tissue stem cell compartments.

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“…In this regard, p53-inducible gene PTEN (Stambolic et al, 2001) or Siah-1L (Matsuzawa and Reed, 2001;Iwai et al, 2004) reduces cellular levels of b-catenin. Absence of PTEN protein suppresses the phosphorylation of b-catenin via inactivation of GSK3b.…”

Section: Ccdc85b Competes With B-catenin For Tcf4mentioning

confidence: 99%

Coiled-coil domain containing 85B suppresses the β-catenin activity in a p53-dependent manner

et al. 2007

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Aberrant accumulation of b-catenin is closely related to carcinogenesis. Mutations in the p53 gene are reported to induce the aberrant accumulation of b-catenin in the absence of dysfunction in the glycogen synthase kinase 3b (GSK3b)-mediated degradation pathway, but the mechanism remains incompletely understood. Here, we show that human coiled-coil domain containing 85B (CCDC85B) is induced by p53 and regulates b-catenin activity via interaction with the T-cell factor 4 in the nucleus. Moreover, CCDC85B enhances the degradation of b-catenin and suppresses tumor cell growth. In conclusion, we revealed that CCDC85B-induced degradation of b-catenin is independent of GSK3b and other p53-inducible products, Siah-1L, suggesting that CCDC85B constitutes the one of the frameworks of p53-induced multiple regulatory pathways for b-catenin activity.

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Regulation of PTEN Transcription by p53

Cited by 828 publications

References 29 publications

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

Id-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition

How does suppression of IGF-1 signaling by DNA damage affect aging and longevity?

Coiled-coil domain containing 85B suppresses the β-catenin activity in a p53-dependent manner

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