SOX5 controls cell cycle progression in neural progenitors by interfering with the WNT–β‐catenin pathway

Martínez-Morales, Patricia L.; Quiroga, Alejandra C.; Barbas, Julio A.; Morales, Aixa V.

doi:10.1038/embor.2010.61

Cited by 63 publications

(77 citation statements)

References 19 publications

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“…4C and data not shown). In light of the evidence that Sox5 regulated p27 protein levels via the Akt or β-catenin pathway [18,31], we further examined the levels of phosphorylated and total Akt and β-catenin in transduced human multiple myeloma cells. We found that overexpression of either Sox5-BLM or L-Sox5 caused robust up-regulation of the total protein levels of β-catenin, but not Akt (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, Sox5 suppresses PDGFB-induced glioma development in Ink4a -/- mice [31]. Interestingly, increased levels of p27 upon Sox5 expression were also observed in PDGFB-induced glioma of Ink4a -/- mice and in chicken developing neurons [18,31]. However, overexpression of Sox5 results in a decrease in the levels of the dephosphorylated active form of β-catenin in chicken developing neurons [18], but an increase in the levels of β-catenin in human multiple myeloma cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the long isoform of Sox5 (L-Sox5) is expressed in multiple tissues, including the cartilage, heart, brain, kidney, lung, and skeletal muscle [11-14]. It has been shown that L-Sox5 plays important roles in regulating diverse processes of embryonic development and cell fate determination, including chondrogenesis [15], notochord and joint development [16,17], neural crest generation [18], oligodendrogenesis [19], melanogenesis [20], lung development [14], and the sequential generation of cortical neurons [21,22]. Sox5 proteins achieve these developmental roles by modulating cell proliferation, survival, differentiation, or terminal maturation in different cell lineages [8].…”

Section: Introductionmentioning

confidence: 99%

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Expression and function of a novel isoform of Sox5 in malignant B cells

et al. 2014

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Using a mouse model with the tumor suppressor TRAF3 deleted from B cells, we identified Sox5 as a gene strikingly up-regulated in B lymphomas. Sox5 proteins were not detected in normal or premalignant TRAF3-/-B cells even after treatment with B cell stimuli. The Sox5 expressed in TRAF3-/-B lymphomas represents a novel isoform of Sox5, and was localized in the nucleus of malignant B cells. Overexpression of Sox5 inhibited cell cycle progression, and up-regulated the protein levels of p27 and β-catenin in human multiple myeloma cells. Together, our findings indicate that Sox5 regulates the proliferation of malignant B cells.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression and function of a novel isoform of Sox5 in malignant B cells

et al. 2014

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“…However, the maintenance of proliferation does not always prevent cells from differentiating (Dyer and Cepko, 2000). Sox5 causes premature cell cycle exit in neural progenitor cells in the chick spinal cord, but also prevents differentiation (Martinez-Morales et al, 2010). Although we have shown that Sox17 regulates the promoters of myelin genes (Sohn et al, 2006), other components of the pathway e.g.…”

Section: Discussionmentioning

confidence: 99%

SRY-Box Containing Gene 17 Regulates the Wnt/β-Catenin Signaling Pathway in Oligodendrocyte Progenitor Cells

Chew¹,

Shen²,

Ming³

et al. 2011

J. Neurosci.

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The SRY-box (Sox) transcription factors regulate oligodendrocyte differentiation, but their signaling targets are largely unknown. We have identified a major signal transduction pathway regulated by Sox17 in the oligodendrocyte lineage. Microarray analysis in oligodendrocyte progenitor cells (OPCs) after Sox17 attenuation revealed upregulated genes associated with cell cycle control and activation of the Wnt/beta-catenin-pathway. Sox17 knockdown also increases the levels of cyclinD1, Axin2 and activated beta-catenin. In OPCs, the expression pattern of Sox17, cyclinD1 and sFRP1 in the presence of PDGF was coordinately accelerated by addition of thyroid hormone, indicating differentiation-induced regulation of Sox17 targets. In developing white matter, decreased total beta-catenin, activated beta-catenin, and cyclinD1 levels coincided with the peak of Sox17 expression, and immunoprecipitates showed a developmentally-regulated interaction between Sox17, TCF4 and beta-catenin proteins. In OPCs, PDGF stimulated phosphorylation of GSK3beta and the Wnt co-receptor LRP6, and enhanced beta-catenin-dependent gene expression. Sox17 overexpression inhibited PDGF-induced TOPFLASH and cyclinD1 promoter activity, and decreased endogenous cyclinD1, activated beta-catenin (ABC) as well as total beta-catenin levels. Recombinant Sox17 prevented Wnt3a from repressing myelin protein expression, and inhibition of Sox17-mediated proteasomal degradation of beta-catenin blocked myelin protein induction. These results indicate that Sox17 suppresses cyclinD1 expression and cell proliferation by directly antagonizing beta-catenin, whose activity in OPCs is stimulated not only by Wnt3a, but also by PDGF. Our identification of downstream targets of Sox17 thus defines signaling pathways and molecular mechanisms in OPCs that are regulated by Sox17 during cell cycle exit and the onset of differentiation in oligodendrocyte development.

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“…In contrast, the long isoform of Sox5 (L-Sox5) is expressed in multiple tissues, including the cartilage, heart, brain, kidney, lung, and skeletal muscle [29,31,32]. L-Sox5 has been shown to play important roles in regulating processes of embryonic development and cell fate determination, including chondrogenesis [33], neural crest development [34,35], oligodendrogenesis [36], lung development [32], and generation of cortical neurons [27]. Sox5 proteins achieve these developmental roles by modulating cell proliferation, survival, differentiation, or terminal maturation in different cell lineages [24].…”

Section: Introductionmentioning

confidence: 94%

Expressions of Sox9, Sox5, and Sox13 transcription factors in mice testis during postnatal development

2015

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SRY-related box (Sox) transcription factors are conserved among vertebrate species. These proteins regulate multiple processes including sex determination and testis differentiation of the male embryo. Although members of the Sox family have been identified in pre- and postnatal Sertoli cells, they have never been characterized in adult Leydig cells. The objectives of this research were to identify expressions of Sox9, Sox5, and Sox13 in mice Leydig cell cultures and to establish their expression profiles in postnatal mice testes at different developmental stages. Methods used include Western blots and qPCR of stimulated MA-10 cell cultures and whole mice testes. Sox9, Sox5, and Sox13 proteins were detected in MA-10 cells as well as whole mouse testis. Although Sox9, Sox5, and Sox13 mRNA levels from whole mice testes tended to increase according to postnatal development, these results were not significant. Sox members were also detected in whole mice testis by Western Blot. However, Sox9, Sox5, and Sox13 protein expressions remained relatively constant during postnatal development from postnatal (P) day 60 to P365. Being newly characterized in the mouse testis, Sox13 was mainly localized by immunofluorescence within the nuclei of cells from seminiferous tubules, possibly spermatocytes and Sertoli cells. In addition, Sox9, Sox5, and Sox13 proteins were characterized in the nuclei of MA-10 Leydig cell cultures. Their expressions and transcriptional activities remained unaffected by activators of the cAMP/PKA pathway. Thus, Sox9, Sox5, and Sox13 transcription factors are expressed in postnatal testis and may regulate multiple functions such as steroidogenesis and spermatogenesis.

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SOX5 controls cell cycle progression in neural progenitors by interfering with the WNT–β‐catenin pathway

Cited by 63 publications

References 19 publications

Expression and function of a novel isoform of Sox5 in malignant B cells

Expression and function of a novel isoform of Sox5 in malignant B cells

SRY-Box Containing Gene 17 Regulates the Wnt/β-Catenin Signaling Pathway in Oligodendrocyte Progenitor Cells

Expressions of Sox9, Sox5, and Sox13 transcription factors in mice testis during postnatal development

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