Prolyl isomerase Pin1 and protein kinase HIPK2 cooperate to promote cortical neurogenesis by suppressing Groucho/TLE:Hes1-mediated inhibition of neuronal differentiation
Copyright policy )Prolyl isomerase Pin1 and protein kinase HIPK2 cooperate to promote cortical neurogenesis by suppressing Groucho/TLE:Hes1-mediated inhibition of neuronal differentiation
The Groucho/transducin-like Enhancer of split 1 (Gro/TLE1):Hes1 transcriptional repression complex acts in cerebral cortical neural progenitor cells to inhibit neuronal differentiation. The molecular mechanisms that regulate the anti-neurogenic function of the Gro/TLE1:Hes1 complex during cortical neurogenesis remain to be defined. Here we show that prolyl isomerase Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) and homeodomain-interacting protein kinase 2 (HIPK2) are expressed in cortical neural progenitor cells and form a complex that interacts with the Gro/TLE1:Hes1 complex. This association depends on the enzymatic activities of both HIPK2 and Pin1, as well as on the association of Gro/TLE1 with Hes1, but is independent of the previously described Hes1-activated phosphorylation of Gro/TLE1. Interaction with the Pin1:HIPK2 complex results in Gro/TLE1 hyperphosphorylation and weakens both the transcriptional repression activity and the anti-neurogenic function of the Gro/TLE1:Hes1 complex. These results provide evidence that HIPK2 and Pin1 work together to promote cortical neurogenesis, at least in part, by suppressing Gro/TLE1:Hes1-mediated inhibition of neuronal differentiation.
Neurogenesis, Basic Helix-Loop-Helix Transcription Factor, cerebral cortex; Groucho/transducin-like Enhancer of split; Hes1; HIPK2; neuronal differentiation; Pin1; Animals; Basic Helix-Loop-Helix Transcription Factors; Carrier Proteins; Cell Differentiation; Cell Line, Tumor; Cells, Cultured; Cerebral Cortex; HEK293 Cells; Homeodomain Proteins; Humans; Mice; Naphthoquinones; Neural Stem Cells; Peptidylprolyl Isomerase; Protein-Serine-Threonine Kinases; Repressor Proteins; Tretinoin; Neurogenesis; Cell Biology; Molecular Biology; Medicine (all), Tretinoin, HIPK2, Protein-Serine-Threonine Kinase, Protein Serine-Threonine Kinases, Mice, Pin1, HEK293 Cell, Naphthoquinone, Neural Stem Cells, cerebral cortex; Groucho/transducin-like Enhancer of split; Hes1; HIPK2; neuronal differentiation; Pin1, Cell Line, Tumor, Basic Helix-Loop-Helix Transcription Factors, Groucho/transducin-like Enhancer of split, Animals, Humans, Neural Stem Cell, neuronal differentiation, Molecular Biology, Cells, Cultured, Cerebral Cortex, Homeodomain Proteins, Animal, Medicine (all), Homeodomain Protein, Cell Differentiation, Cell Biology, Repressor Protein, Peptidylprolyl Isomerase, Hes1, NIMA-Interacting Peptidylprolyl Isomerase, Repressor Proteins, HEK293 Cells, cerebral cortex, Transcription Factor HES-1, Neurogenesi, Carrier Protein, Carrier Proteins, Human, Naphthoquinones
Neurogenesis, Basic Helix-Loop-Helix Transcription Factor, cerebral cortex; Groucho/transducin-like Enhancer of split; Hes1; HIPK2; neuronal differentiation; Pin1; Animals; Basic Helix-Loop-Helix Transcription Factors; Carrier Proteins; Cell Differentiation; Cell Line, Tumor; Cells, Cultured; Cerebral Cortex; HEK293 Cells; Homeodomain Proteins; Humans; Mice; Naphthoquinones; Neural Stem Cells; Peptidylprolyl Isomerase; Protein-Serine-Threonine Kinases; Repressor Proteins; Tretinoin; Neurogenesis; Cell Biology; Molecular Biology; Medicine (all), Tretinoin, HIPK2, Protein-Serine-Threonine Kinase, Protein Serine-Threonine Kinases, Mice, Pin1, HEK293 Cell, Naphthoquinone, Neural Stem Cells, cerebral cortex; Groucho/transducin-like Enhancer of split; Hes1; HIPK2; neuronal differentiation; Pin1, Cell Line, Tumor, Basic Helix-Loop-Helix Transcription Factors, Groucho/transducin-like Enhancer of split, Animals, Humans, Neural Stem Cell, neuronal differentiation, Molecular Biology, Cells, Cultured, Cerebral Cortex, Homeodomain Proteins, Animal, Medicine (all), Homeodomain Protein, Cell Differentiation, Cell Biology, Repressor Protein, Peptidylprolyl Isomerase, Hes1, NIMA-Interacting Peptidylprolyl Isomerase, Repressor Proteins, HEK293 Cells, cerebral cortex, Transcription Factor HES-1, Neurogenesi, Carrier Protein, Carrier Proteins, Human, Naphthoquinones
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