TGIF Inhibits Retinoid Signaling

Bartholin, Laurent; Powers, Shannon; Melhuish, Tiffany A.; Lasse, Samuel; Weinstein, Michael; Wotton, David

doi:10.1128/mcb.26.3.990-1001.2006

Cited by 109 publications

(139 citation statements)

References 53 publications

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“…Cells were grown into 24-well plates and transfected with a pGL2 Promoter vector containing five DR1 consensus RAREs 46 (generously provided by D. Wotton, University of Virginia) and co-transfected with a b-galactosidase plasmid as a transfection control. Medium was removed from the wells and cells were washed once with 1 Â PBS.…”

Section: Methodsmentioning

confidence: 99%

Stra6, a retinoic acid-responsive gene, participates in p53-induced apoptosis after DNA damage

et al. 2013

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Stra6 is the retinoic acid (RA)-inducible gene encoding the cellular receptor for holo-retinol binding protein. This transmembrane protein mediates the internalization of retinol, which then upregulates RA-responsive genes in target cells. Here, we show that Stra6 can be upregulated by DNA damage in a p53-dependent manner, and it has an important role in cell death responses. Stra6 expression induced significant amounts of apoptosis in normal and cancer cells, and it was also able to influence p53-mediated cell fate decisions by turning an initial arrest response into cell death. Moreover, inhibition of Stra6 severely compromised p53-induced apoptosis. We also found that Stra6 induced mitochondria depolarization and accumulation of reactive oxygen species, and that it was present not only at the cellular membrane but also in the cytosol. Finally, we show that these novel functions of Stra6 did not require downstream activation of RA signalling. Our results present a previously unknown link between the RA and p53 pathways and provide a rationale to use retinoids to upregulate Stra6, and thus enhance the tumour suppressor functions of p53. This may have implications for the role of vitamin A metabolites in cancer prevention and treatment.

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Section: Methodsmentioning

confidence: 99%

Stra6, a retinoic acid-responsive gene, participates in p53-induced apoptosis after DNA damage

et al. 2013

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“…Iro7 (also known as Irx7 -Zebrafish Information Network) is a TALE homeodomain protein expressed in the anterior hindbrain that represses vhnf1 expression anterior to the r4-r5 boundary (Lecaudey et al, 2004). Other TALE homeodomain proteins have been shown to repress transcription from retinoid-responsive elements by binding to RXR retinoid receptors and recruiting general corepressors to the complex (Bartholin et al, 2006). Thus, Iro7 may compensate for Cyp26b1 and Cyp26c1 by directly suppressing RAresponsive gene expression anterior to the r4-r5 boundary.…”

Section: Research Article Cyp26 Enzymes In Hindbrain Developmentmentioning

confidence: 99%

Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development

et al. 2007

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Retinoic acid (RA) is essential for normal vertebrate development,including the patterning of the central nervous system. During early embryogenesis, RA is produced in the trunk mesoderm through the metabolism of vitamin A derived from the maternal diet and behaves as a morphogen in the developing hindbrain where it specifies nested domains of Hox gene expression. The loss of endogenous sources of RA can be rescued by treatment with a uniform concentration of exogenous RA, indicating that domains of RA responsiveness can be shaped by mechanisms other than the simple diffusion of RA from a localized posterior source. Here, we show that the cytochrome p450 enzymes of the Cyp26 class, which metabolize RA into polar derivatives,function redundantly to shape RA-dependent gene-expression domains during hindbrain development. In zebrafish embryos depleted of the orthologs of the three mammalian CYP26 genes CYP26A1, CYP26B1 and CYP26C1, the entire hindbrain expresses RA-responsive genes that are normally restricted to nested domains in the posterior hindbrain. Furthermore,we show that Cyp26 enzymes are essential for exogenous RA to rescue hindbrain patterning in RA-depleted embryos. We present a `gradient-free' model for hindbrain patterning in which differential RA responsiveness along the hindbrain anterior-posterior axis is shaped primarily by the dynamic expression of RA-degrading enzymes.

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“…The TGIF gene encodes a homeodomain protein that interacts with TGF-beta-activated Smad proteins [145] and acts as a contextindependent transcriptional repressor [146]. Furthermore, TGIF1 interacts with RXR and A c c e p t e d M a n u s c r i p t 21 recruits transcriptional co-repressors [147]. The closely related TGIF2 functions similarly to TGIF1 [148,149].…”

Section: Tgif1mentioning

confidence: 99%

Transcriptional co-factors and hepatic energy metabolism

Sommerfeld

Krones-Herzig

Herzig

2011

Molecular and Cellular Endocrinology

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After binding to their cognate DNA-binding partner, transcriptional co-factors exert their function through the recruitment of enzymatic, chromatin-modifying activities. In turn, the assembly of co-factor-associated multi-protein complexes efficiently impacts target gene expression. Recent advances have established transcriptional co-factor complexes as a critical regulatory level in energy homeostasis and aberrant co-factor activity has been linked to the pathogenesis of severe metabolic disorders including obesity, type 2 diabetes and other components of the Metabolic Syndrome. The liver represents the key peripheral organ for the maintenance of systemic energy homeostasis, and aberrations in hepatic glucose and lipid metabolism have been causally linked to the manifestation of disorders associated with the Metabolic Syndrome. Therefore, this review focuses on the role of distinct classes of transcriptional co-factors in hepatic glucose and lipid homeostasis, emphasizing pathwayspecific functions of these co-factors under physiological and pathophysiological conditions.

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TGIF Inhibits Retinoid Signaling

Cited by 109 publications

References 53 publications

Stra6, a retinoic acid-responsive gene, participates in p53-induced apoptosis after DNA damage

Stra6, a retinoic acid-responsive gene, participates in p53-induced apoptosis after DNA damage

Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development

Transcriptional co-factors and hepatic energy metabolism

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