sel-10, a negative regulator of lin-12 activity inCaenorhabditis elegans, encodes a member of the CDC4 family of proteins

  1. E. Jane Albert Hubbard1,
  2. Guangyu Wu2,
  3. Jan Kitajewski2, and
  4. Iva Greenwald1,3
  1. 1Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute and 2Department of Pathology and Center for Reproductive Sciences, Columbia University College of Physicians and Surgeons, New York, New York 10032 USA

Abstract

Mutations that influence lin-12 activity inCaenorhabditis elegans may identify conserved factors that regulate the activity of lin-12/Notch proteins. We describe genetic evidence indicating that sel-10 is a negative regulator of lin-12/Notch-mediated signaling in C. elegans. Sequence analysis shows that SEL-10 is a member of the CDC4 family of proteins and has a potential human ortholog. Coimmunoprecipitation data indicate that C. elegansSEL-10 complexes with LIN-12 and with murine Notch4. We propose that SEL-10 promotes the ubiquitin-mediated turnover of LIN-12/Notch proteins, and discuss potential roles for the regulation of lin-12/Notch activity bysel-10 in cell fate decisions and tumorigenesis.

Keywords

Footnotes

  • 3 Corresponding author.

  • E-MAIL greenwald{at}cuccfa.ccc.columbia.edu; FAX (212) 305-1721.

    • Received July 28, 1997.
    • Accepted September 22, 1997.
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