Id proteins in epithelial cells

Coppé, Jean‐Philippe; Smith, Andrew P.; Desprez, Pierre-Yves

doi:10.1016/s0014-4827(03)00014-4

Cited by 66 publications

(52 citation statements)

References 144 publications

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“…For instance, Crowe et al (13) reported that E2F1, a transcription factor involved in activation of genes associated with the cell cycle, binds to the human telomerase reverse transcriptase promoter and represses its activity. On the contrary, E2F4 and Id2 are positively related to the activity of telomerase (11,12). We find here that intracellular glutathione activates both Id2 and E2F4 and that on the contrary it inactivates E2F1.…”

Section: Modulation Of Glutathione Levels Affects the Rate Of Cell Grmentioning

confidence: 42%

Glutathione Regulates Telomerase Activity in 3T3 Fibroblasts

Borrás¹,

Esteve²,

Viña

et al. 2004

Journal of Biological Chemistry

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Changes in telomerase activity have been associated either with cancer, when activity is increased, or with cell cycle arrest when it is decreased. We report that glutathione, a physiological antioxidant present at high intracellular concentrations, regulates telomerase activity in cells in culture. Telomerase activity increases in 3T3 fibroblasts before exponential cell growth. The peak of telomerase activity takes place 24 h after plating and coincides with the maximum levels of glutathione in the cells. When cells are treated with buthionine sulfoximine, which decreases glutathione levels in cells, telomerase activity decreases by 60%, and cell growth is delayed. Glutathione depletion inhibits expression of E2F4 and Id2, which regulate the cell cycle. When glutathione levels are restored after incubation with glutathione monoethylester, telomerase activity and the cell cyclerelated proteins return to control values. To discover the effect of glutathione redox status on the telomerase multicomplex structure, we incubated protein extracts from fibroblasts with different glutathione redox buffers. Telomerase activity is maximal under reduced conditions i.e. when the reduced/oxidized glutathione ratio is high. Consequently glutathione concentration parallels telomerase activity. These results underscore the main role of glutathione in the control of telomerase activity and of the cell cycle.The eukaryotic chromosomes are capped by telomeres, which consist of telomeric DNA repeated in tandem, associated with several proteins. These structures play an important role in the stability and the complete replication of the chromosomes. Conventional DNA polymerases cannot fully replicate the 3Ј-end of the lagging strand of linear molecules, and therefore in every cell division telomeric sequences are lost (1).Telomerase is an important enzyme that ensures the maintenance of normal telomere length. This activity is high in human cancers (2) but virtually absent in normal tissues, except germinal cells (3). Telomerase regulation is not well understood, but its changes are related to both cancer and aging (4).Glutathione (GSH) 1 is the most abundant non-protein thiol in cells. Its activity ranges in the level of 5 mol/gram of tissue (5), i.e. higher than that of glucose. It has a critical role in the maintenance thiol redox status in cells. Changes in the redox ratio (GSH/GSSG) of GSH are relevant to the maintenance of enzyme activities (6). The aim of this work was to study the role of glutathione in the regulation of the telomerase activity in cells. We found that cellular glutathione levels correlate with telomerase activity in 3T3 fibroblasts. The peak of telomerase activity coincides with the GSH peak. Depletion of GSH with buthionine sulfoximine (BSO) reduces the telomerase activity and that of regulators of the cell cycle such as Id2 and E2F4 after 24 and 48 h of treatment. Furthermore, changes in the GSH/GSSG redox potential modulate telomerase activity. We concluded that the GSH levels in cells and subsequently oxi...

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Section: Modulation Of Glutathione Levels Affects the Rate Of Cell Grmentioning

confidence: 42%

Glutathione Regulates Telomerase Activity in 3T3 Fibroblasts

Borrás¹,

Esteve²,

Viña

et al. 2004

Journal of Biological Chemistry

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“…Ids, a family of four (Id1-Id4) naturally occurring dominantnegative transcription factors that mediate their effects primarily through their highly conserved HLH domain (Benezra et al, 1990;Norton, 2000), are thought to be important regulators of a range of epithelial cell types (Coppe et al, 2003). These proteins have been shown to bind to, and prevent DNA binding by, transcription factors of the bHLH, Pax and ETS families (Benezra et al, 1990;Yates et al, 1999;Roberts et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

XenopusId3 is required downstream of Myc for the formation of multipotent neural crest progenitor cells

et al. 2005

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“…Resistance to growth inhibition by TGF-ß1 has been considered an important step in tumorigenesis and contributes to the development of many tumor types (3,4). Recently, Id1 (inhibitors of DNA binding or differentiation) was revealed to be one of the direct TGF-ß1 target genes (5). Specifically in epithelial cells, Id1 expression can be inhibited through the TGF-ß1-responsive Smad3-activated transcriptional repressor, ATF3, which binds to the ATF/CREB site on the Id promoter, repressing Smad-initiated transcription.…”

Section: Introductionmentioning

confidence: 99%

TGF-β1-induced cell growth arrest and partial differentiation is related to the suppression of Id1 in human hepatoma cells

Damdinsuren¹,

Nagano²,

Kondo³

et al. 2006

Oncol Rep

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Abstract. Transforming growth factor beta 1 (TGF-ß1) is a proposed regulator of Ids (inhibitors of DNA binding/differentiation) gene expression in epithelial cells. We previously reported that Id proteins are variously expressed in human hepatocellular carcinomas (HCC). However, the mechanism of regulation of Ids in HCC remains obscure. Here, we examined the relationship between Id1 and TGF-ß1 in four HCC cell lines, and studied the changes in cell proliferation, cell cycle and differentiation. The four HCC cell lines expressed Id1, TGF-ß1 and their receptors at various levels. TGF-ß1 strongly inhibited the growth of HuH7 cells, while the growth inhibition was moderate in PLC/PRF/5, and was not observed in HLE and HLF cell lines. TGF-ß1-induced growth inhibition in HuH7 cells was associated with cell accumulation in the G1 phase and partial induction of differentiation (with reduction of AFP and AFP-L3). Induction by TGF-ß1 dose-dependently suppressed Id1 expression in HuH7 cells; 1 ng/ml TGF-ß1 inhibited Id1 by 84.0 and 78.6% that of the untreated control at transcriptional and protein levels, respectively. HLE and HLF cells, which did not exhibit a TGF-ß1 growth inhibitory effect, lacked TGF-ß receptors and Id1 expression was not altered. In PLC/PRF/ 5 cells, Id1 augmentation was not observed in response to TGF-ß1, indicating that TGF-ß1-induced growth inhibition was not related to Id1 in this cell line. Our results suggest that, in some HCC cells, the pathway of suppression of Id1 by TGF-ß1 may be important in TGF-ß1-induced growth inhibition and partial differentiation.

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Id proteins in epithelial cells

Cited by 66 publications

References 144 publications

Glutathione Regulates Telomerase Activity in 3T3 Fibroblasts

Glutathione Regulates Telomerase Activity in 3T3 Fibroblasts

XenopusId3 is required downstream of Myc for the formation of multipotent neural crest progenitor cells

TGF-β1-induced cell growth arrest and partial differentiation is related to the suppression of Id1 in human hepatoma cells

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