Accession Number:

ADA394195

Title:

Notch4 Ligands in Mammary Gland Development and Tumorigenesis

Descriptive Note:

Final rept. 1 Aug 1997-31 Jul 2000

Corporate Author:

COLUMBIA UNIV NEW YORK

Personal Author(s):

Report Date:

2000-08-01

Pagination or Media Count:

83.0

Abstract:

Notch receptors play important roles in both normal animal development and pathogenesis. We show that the CDC4 family protein SEL-l0 negatively regulates Notch receptor activity by targeting the intracellular domain of Notch receptors for ubiquitin-mediated protein degradation. The WD40 repeats of SEL-l0 interact with the C-terminal domain of Notch receptors. SEL-l0 binds preferentially to a phosphorylated form of Notch4 in cells, and mediates ubiquitination of Notch proteins in vitro. Blocking endogenous SEL-l0 activity by over-expression of a dominant-negative form of SEL-l0 with only the WD40 repeats leads to stabilization of the intracellular domain of Notch and up-regulation of Notch induced reporter activation.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE