Notch4 Ligands in Mammary Gland Development and Tumorigenesis
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA394195
Entities
People
- Guangyu Wu
Organizations
- Columbia University