title: Prolyl isomerase Pin1 and protein kinase HIPK2 cooperate to promote cortical neurogenesis by suppressing Groucho/TLE:Hes1-mediated inhibition of neuronal differentiation.
abstract: 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.
authors.affiliation: 1] Montreal Neurological Institute, McGill University, 3801 rue University, Montreal, Quebec H3A2B4, Canada [2] Department of Oncohematology, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Ciarapica
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 rue University, Montreal, Quebec H3A2B4, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Methot
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 rue University, Montreal, Quebec H3A2B4, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 rue University, Montreal, Quebec H3A2B4, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Lo
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 rue University, Montreal, Quebec H3A2B4, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Dali
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 rue University, Montreal, Quebec H3A2B4, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Buscarlet
authors.affiliation: 1] Department of Oncohematology, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy [2] University of Pavia, Pavia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: 1] Laboratorio Nazionale CIB, Area Science Park, Trieste, Italy [2] Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste, Italy.
authors.forename: G
authors.initials: G
authors.lastname: del Sal
authors.affiliation: Department of Oncohematology, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Rota
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 rue University, Montreal, Quebec H3A2B4, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Stifani
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009285:Naphthoquinones / Q000494:pharmacology; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D000072056:Transcription Factor HES-1; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D018398:Homeodomain Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009285:Naphthoquinones; D019696:Peptidylprolyl Isomerase; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; D014212:Tretinoin; C078493:HES1 protein, human; C115114:HIPK2 protein, human; C000606846:PIN1 protein, human; C000606850:Pin1 protein, mouse; C005134:juglone