title: Return to quiescence of mouse neural stem cells by degradation of a proactivation protein.
abstract: Quiescence is essential for long-term maintenance of adult stem cells. Niche signals regulate the transit of stem cells from dormant to activated states. Here, we show that the E3-ubiquitin ligase Huwe1 (HECT, UBA, and WWE domain-containing 1) is required for proliferating stem cells of the adult mouse hippocampus to return to quiescence. Huwe1 destabilizes proactivation protein Ascl1 (achaete-scute family bHLH transcription factor 1) in proliferating hippocampal stem cells, which prevents accumulation of cyclin Ds and promotes the return to a resting state. When stem cells fail to return to quiescence, the proliferative stem cell pool becomes depleted. Thus, long-term maintenance of hippocampal neurogenesis depends on the return of stem cells to a transient quiescent state through the rapid degradation of a key proactivation factor.
authors.affiliation: The Francis Crick Institute-Mill Hill Laboratory, NW7 1AA, London, UK. noelia.urban@crick.ac.uk francois.guillemot@crick.ac.uk.
authors.forename: Noelia
authors.initials: N
authors.lastname: Urbán
authors.affiliation: The Francis Crick Institute-Mill Hill Laboratory, NW7 1AA, London, UK.
authors.forename: Debbie L C
authors.initials: DL
authors.lastname: van den Berg
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR 3347, INSERM U1021, 91405, Orsay, France. Université Paris Sud, Université Paris Saclay, CNRS UMR 3347, INSERM U1021, 91405, Orsay, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Forget
authors.affiliation: The Francis Crick Institute-Mill Hill Laboratory, NW7 1AA, London, UK.
authors.forename: Jimena
authors.initials: J
authors.lastname: Andersen
authors.affiliation: Proteomics Center, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, Netherlands.
authors.forename: Jeroen A A
authors.initials: JA
authors.lastname: Demmers
authors.affiliation: The Francis Crick Institute-Mill Hill Laboratory, NW7 1AA, London, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Hunt
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR 3347, INSERM U1021, 91405, Orsay, France. Université Paris Sud, Université Paris Saclay, CNRS UMR 3347, INSERM U1021, 91405, Orsay, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Ayrault
authors.affiliation: The Francis Crick Institute-Mill Hill Laboratory, NW7 1AA, London, UK. noelia.urban@crick.ac.uk francois.guillemot@crick.ac.uk.
authors.forename: François
authors.initials: F
authors.lastname: Guillemot
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D049109:Cell Proliferation; D006624:Hippocampus / Q000166:cytology / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis; D055550:Protein Stability; D059748:Proteolysis; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; C499317:Ascl1 protein, mouse; C502831:Huwe1 protein, mouse