Glucocorticoid Hormones Decrease Proliferation of Embryonic Neural Stem Cells through Ubiquitin-Mediated Degradation of Cyclin D1

Sundberg, Maria; Savola, Suvi; Hienola, Anni; Korhonen, Laura; Lindholm, Dan

doi:10.1523/jneurosci.4906-05.2006

Cited by 105 publications

(112 citation statements)

References 38 publications

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“…S3C). GC effects on neuronal migration and ubiquitin-proteasome mediated degradation have previously been observed in neural stem cells (9,36) and may be influenced by Cav-1. To summarize, in addition to identifying many novel primary GC responsive genes in NPSCs, our microarray data implicated Cav-1 as a modulator of both rapid signaling and genomic action of GR.…”

Section: Resultsmentioning

confidence: 76%

“…The contribution of rapid GR signaling to the antiproliferative effects of GCs exerted on a variety of tissue and cell types remains unresolved (9,11,16). Since rapid signaling effects of GCs on MAPK activation and GJIC are lost upon Cav-1 deletion in embryonic NPSCs (17), we tested whether the antiproliferative effects of GCs were altered in Cav-1 KO NPSCs.…”

Section: Resultsmentioning

confidence: 99%

“…The most prominent pathways defined by the GR transcriptome in C57 NPSCs regulated cell cycle progression and contain a number of genes that could contribute to the antiproliferative effects of GCs (9,16,17). Notably, one validated GR target gene, Sgk-1, is required for the antiproliferative effects of GC in embryonic mouse NPSCs (the present study) and a human hippocampal progenitor cell line (19) but did not reach significance as GC regulated in our microarray analysis or that reported in hippocampal progenitors (see Table S2 in the supplemental material) (23).…”

Section: Discussionmentioning

confidence: 99%

“…For example, in rat embryonic neural stem cells, GCs decreased proliferation by enhanced degradation of the cell cycle regulator cyclin D1 (9). In the mouse cerebellum, neonatal treatment with Dex increased apoptosis of the neural progenitor cells within the extra granule cell layer and decreased overall numbers of internal granule layer neurons (10).…”

mentioning

confidence: 99%

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Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Peffer

Chandran

Luthra

et al. 2014

Molecular and Cellular Biology

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While glucocorticoids (GCs) are used clinically to treat many conditions, their neonatal and prenatal usage is increasingly controversial due to reports of delayed adverse outcomes, especially their effects on brain development. Such alterations may reflect the impact of GCs on neural progenitor/stem cell (NPSC) function. We previously demonstrated that the lipid raft protein caveolin-1 (Cav-1) was required for rapid GC signaling in embryonic mouse NPSCs operating through plasma membranebound glucocorticoid receptors (GRs). We show here that genomic GR signaling in NPSCs requires Cav-1. Loss of Cav-1 impacts the transcriptional response of many GR target genes (e.g., the serum-and glucocorticoid-regulated kinase 1 gene) that are likely to mediate the antiproliferative effects of GCs. Microarray analysis of wild-type C57 or Cav-1-deficient NPSCs identified approximately 100 genes that are differentially regulated by GC treatment. These changes in hormone responsiveness in Cav-1 knockout NPSCs are associated with the loss of GC-regulated phosphorylation of GR at serine 211 but not at serine 226. Chromatin recruitment of total GR to regulatory regions of target genes such as Fkbp-5, RhoJ, and Sgk-1, as well as p211-GR recruitment to Sgk-1, are compromised in Cav-1 knockout NPSCs. Cav-1 is therefore a multifunctional regulator of GR in NPSCs influencing both rapid and genomic action of the receptor to impact cell proliferation.

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Section: Resultsmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Peffer

Chandran

Luthra

et al. 2014

Molecular and Cellular Biology

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“…In a different experimental system, glucocorticoid-induced decline in proliferation of neural stem cells was abrogated in the presence of 0.5 mM of a potent proteasomal inhibitor MG132, reflecting an involvement of the ubiquitin proteasomal pathway (Sundberg et al, 2006). Furthermore, Id2 has been identified as a potential substrate for some E3 ubiquitin ligase complexes and, thus, can be targeted for proteasomal degradation (Lasorella et al, 2006).…”

Section: Resultsmentioning

confidence: 99%

Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes

et al. 2007

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We investigated the effect of all-trans-retinoic acid (atRA) on proliferation in several human skin cell lines and found that antiproliferative potency of atRA correlated with the endogenous activity of canonical Wnt signaling. In HaCaT keratinocytes, we found that atRA significantly suppressed the expression of Id2, a member of the inhibitor of differentiation family of transcription factors that regulate cell growth and differentiation. However, no apparent change in the expression of other Wnt targets, like c-Myc or cyclin D1, was observed. Retinoid-induced Id2 gene suppression was associated with decreased levels of histone H3 and H4 acetylation and histone H3 Lys-4 methylation, and with recruitment of the LSD1 demethylase at the Wnt-response element (WRE) (TCF/LEF-binding site), in the Id2 gene promoter. None of such changes was detected at the WRE of c-Myc and cyclin D1 gene promoters. Inhibition of Id2 by short interfering RNA (siRNA) had a similar effect on the proliferation of HaCaT cells as exposure to atRA, whereas anti-b-catenin siRNA significantly inhibited its antiproliferative effect. These data suggest that downregulation of Id2 gene expression through transcriptional convergence between Wnt and retinoid signaling pathways underlies the antiproliferative effect of retinoids in keratinocytes, and provide evidence of gene-targeted crosstalk between signaling pathways.

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Animal evolution during domestication: the domesticated fox as a model

2009

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Summary We review the evolution of domestic animals, emphasizing the effect of the earliest steps of domestication on its course. Using the first domesticated species, the dog (Canis familiaris) as an illustration, we describe the evolutionary specificities of the historical domestication, such as the high level and wide range of diversity. We suggest that the process of earliest domestication via unconscious and later conscious selection of human-defined behavioral traits may accelerate phenotypic variations. The review is based on the results of the long-term experiment designed to reproduce early mammalian domestication in the silver fox (Vulpes vulpes) selected for tameability, or amenability to domestication. We describe changes in behavior, morphology and physiology that appeared in the fox during its selection for tameability and that were similar to those observed in the domestic dog. Based on the experimental fox data and survey of relevant data, we discuss the developmental, genetic and possible molecular-genetic mechanisms of these changes. We assign the causative role in evolutionary transformation of domestic animals to selection for behavior and to the neurospecific regulatory genes it affects.

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Glucocorticoid Hormones Decrease Proliferation of Embryonic Neural Stem Cells through Ubiquitin-Mediated Degradation of Cyclin D1

Cited by 105 publications

References 38 publications

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes

Animal evolution during domestication: the domesticated fox as a model

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