IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms9763.html
   My bibliography  Save this article

ASPM regulates symmetric stem cell division by tuning Cyclin E ubiquitination

Author

Listed:
  • Mario R. Capecchi

    (University of Utah
    Howard Hughes Medical Institute)

  • Amir Pozner

    (University of Utah
    Present address: Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, USA)

Abstract

We generate a mouse model for the human microcephaly syndrome by mutating the ASPM locus, and demonstrate a premature exhaustion of the neuronal progenitor pool due to dysfunctional self-renewal processes. Earlier studies have linked ASPM mutant progenitor excessive cell cycle exit to a mitotic orientation defect. Here, we demonstrate a mitotic orientation-independent effect of ASPM on cell cycle duration. We pinpoint the cell fate-determining factor to the length of time spent in early G1 before traversing the restriction point. Characterization of the molecular mechanism reveals an interaction between ASPM and the Cdk2/Cyclin E complex, regulating the Cyclin activity by modulating its ubiquitination, phosphorylation and localization into the nucleus, before the cell is fated to transverse the restriction point. Thus, we reveal a novel function of ASPM in mediating the tightly coordinated Ubiquitin- Cyclin E- Retinoblastoma- E2F bistable-signalling pathway controlling restriction point progression and stem cell maintenance.

Suggested Citation

  • Mario R. Capecchi & Amir Pozner, 2015. "ASPM regulates symmetric stem cell division by tuning Cyclin E ubiquitination," Nature Communications, Nature, vol. 6(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9763
    DOI: 10.1038/ncomms9763
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms9763
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms9763?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9763. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.