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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.

SUBMITTER: Urban N

PROVIDER: S-EPMC5321528 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Return to quiescence of mouse neural stem cells by degradation of a proactivation protein.

Urbán Noelia N van den Berg Debbie L C DL Forget Antoine A Andersen Jimena J Demmers Jeroen A A JA Hunt Charles C Ayrault Olivier O Guillemot François F

Science (New York, N.Y.) 20160701 6296

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 accum ...[more]

PMID: 27418510

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