Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Nov;13(11):1365-72.
doi: 10.1038/nn.2644. Epub 2010 Oct 10.

Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun

Joerg D Hoeck  1 , Anett Jandke, Sophia M Blake, Emma Nye, Bradley Spencer-Dene, Sebastian Brandner, Axel Behrens
Affiliations
Free article

Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun

Joerg D Hoeck et al. Nat Neurosci. 2010 Nov.
Free article

Abstract

Neural stem and progenitor cells (NSCs/NPCs) give rise to neurons, astrocytes and oligodendrocytes. However, the mechanisms underlying the decision of a stem cell to either self-renew or differentiate are incompletely understood. We demonstrate here that Fbw7 (F-box and WD repeat domain containing-7), the substrate recognition component of an SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase, is a key regulator of NSC/NPC viability and differentiation. The absence of Fbw7 in the mouse brain caused severely impaired stem cell differentiation and increased progenitor cell death. Fbw7 deficiency resulted in accumulation of two SCF(Fbw7) substrates, the transcription factors active Notch1 and N-terminally phosphorylated c-Jun. Genetic and pharmacological rescue experiments identified c-Jun as a key substrate of Fbw7 in controlling progenitor cell viability, whereas inhibition of Notch signaling alleviated the block in stem cell differentiation. Thus Fbw7 controls neurogenesis by antagonizing Notch and c-Jun N-terminal kinase (JNK)/c-Jun signaling.

PubMed Disclaimer

Comment in

  • The importance of degradation.
    Markus A. Markus A. Nat Neurosci. 2010 Nov;13(11):1311. doi: 10.1038/nn1110-1311. Nat Neurosci. 2010. PMID: 20975753 No abstract available.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Nat Genet. 1999 Mar;21(3):326-9 - PubMed
    1. Development. 1997 Mar;124(6):1139-48 - PubMed
    1. Cancer Biol Ther. 2005 May;4(5):506-8 - PubMed
    1. Neuron. 2004 Jul 8;43(1):57-67 - PubMed
    1. J Biol Chem. 2007 Oct 19;282(42):30901-9 - PubMed

Publication types

MeSH terms