ArticlePloS one2009
Cofactor-activated phosphorylation is required for inhibition of cortical neuron differentiation by Groucho/TLE1.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Systemic degradation of repressive transcription factors gates gene expression and cell fate specification.bioRxiv : the preprint server for biology · 2026Article
- Ssn6 Interacts with Polar Tube Protein 2 and Transcriptional Repressor for RNA Polymerase II: Insight into Its Involvement in the Biological Process of MicrosporidiumJournal of fungi (Basel, Switzerland) · 2023Article
- TLE2 is associated with favorable prognosis and regulates cell growth and gemcitabine sensitivity in pancreatic cancer.Annals of translational medicine · 2020Article
- Downregulation of Bit1 expression promotes growth, anoikis resistance, and transformation of immortalized human bronchial epithelial cells via Erk activation-dependent suppression of E-cadherin.Biochemical and biophysical research communications · 2018Article
- Unraveling the differential dynamics of developmental fate in central and peripheral nervous systems.Scientific reports · 2016Article
- Reinitiation of mRNA translation in a patient with X-linked infantile spasms with a protein-truncating variant in ARX.European journal of human genetics : EJHG · 2016Article
- Prognostic and Clinicopathological Significance of Transducer-Like Enhancer of Split 1 Expression in Gastric Cancer.Journal of gastric cancer · 2016Article
- The Groucho/Transducin-like enhancer of split protein family in animal development.IUBMB life · 2015Review
- TLE1 promotes EMT in A549 lung cancer cells through suppression of E-cadherin.Biochemical and biophysical research communications · 2014Article
- Prolyl isomerase Pin1 and protein kinase HIPK2 cooperate to promote cortical neurogenesis by suppressing Groucho/TLE:Hes1-mediated inhibition of neuronal differentiation.Cell death and differentiation · 2014Article
- A Gro/TLE-NuRD corepressor complex facilitates Tbx20-dependent transcriptional repression.Journal of proteome research · 2013Article
- TLE1 is an anoikis regulator and is downregulated by Bit1 in breast cancer cells.Molecular cancer research : MCR · 2012Article
- Transducin-like enhancer of Split-1 (TLE1) combines with Forkhead box protein G1 (FoxG1) to promote neuronal survival.The Journal of biological chemistry · 2012Article
- Differential effects of a polyalanine tract expansion in Arx on neural development and gene expression.Human molecular genetics · 2012Article
- The unconserved groucho central region is essential for viability and modulates target gene specificity.PloS one · 2012Article
- EAR motif-mediated transcriptional repression in plants: an underlying mechanism for epigenetic regulation of gene expression.Epigenetics · 2011Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTranscriptional co-repressors of the Groucho/transducin-like Enhancer of split (Gro/TLE) family regulate the expression of a variety of genes and are involved in numerous developmental processes in both invertebrate and vertebrate species. More specifically, Gro/TLE1 participates in mechanisms that inhibit/delay the differentiation of cerebral cortex neural progenitor cells into neurons during mammalian forebrain development. The anti-neurogenic function of Gro/TLE1 depends on the formation of protein complexes with specific DNA-binding transcription factors that engage Gro/TLE1 through WRP(W/Y) sequences. Interaction with those transcription partners results in Gro/TLE1 recruitment to selected DNA sites and causes increased Gro/TLE1 phosphorylation. The physiological significance of the latter event, termed "cofactor-activated phosphorylation," had not been determined. Therefore, this study aimed at clarifying the role of cofactor-activated phosphorylation in the anti-neurogenic function of Gro/TLE1. METHODS AND PRINCIPAL
findingsA combination of site-directed mutagenesis, mass spectrometry, biochemistry, primary cell culture, and immunocytochemical assays was utilized to characterize point mutations of Ser-286, a residue that is phosphorylated in vivo and is located within the serine/proline-rich (SP) domain of Gro/TLE1. Mutation of Ser-286 to alanine or glutamic acid does not perturb the interaction of Gro/TLE1 with DNA-binding partners, including the basic helix-loop-helix transcription factor Hes1, a prototypical anti-neurogenic WRP(W/Y) motif protein. Ser-286 mutations do not prevent the recruitment of Gro/TLE1 to DNA, but they impair cofactor-activated phosphorylation and weaken the interaction of Gro/TLE1 with chromatin. These effects are correlated with an impairment of the anti-neurogenic activity of Gro/TLE1. Similar results were obtained when mutations of Ser-289 and Ser-298, which are also located within the SP domain of Gro/TLE1, were analyzed.
conclusionBased on the positive correlation between Gro/TLE1 cofactor-activated phosphorylation and ability to inhibit cortical neuron differentiation, we propose that hyperphosphorylation induced by cofactor binding plays a positive role in the regulation of Gro/TLE1 anti-neurogenic activity.
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