Open Close
Reference
Citation
Vaccari, T., Bilder, D. (2005). The Drosophila tumor suppressor vps25 prevents nonautonomous overproliferation by regulating Notch trafficking.  Dev. Cell 9(5): 687--698.
FlyBase ID
FBrf0190223
Publication Type
Research paper
Abstract

Cell-cell signaling coordinates proliferation of metazoan tissues during development, and its alteration can induce malignant transformation. Endocytosis regulates signaling by controlling the levels and activity of transmembrane receptors, both prior to and following ligand engagement. Here, we identify Vps25, a component of the ESCRT machinery that regulates endocytic sorting of signaling receptors, as an unconventional type of Drosophila tumor suppressor. vps25 mutant cells undergo autonomous neoplastic-like transformation, but they also stimulate nonautonomous cell proliferation. Endocytic trafficking defects in vps25 cells cause endosomal accumulation of the signaling receptor Notch and enhanced Notch signaling. Increased Notch activity leads to ectopic production of the mitogenic JAK-STAT pathway ligand Unpaired, which is secreted from mutant cells to induce overproliferation of the surrounding epithelium. Our data show that defects in endocytic sorting can both transform cells and, through heterotypic signaling, alter the behavior of neighboring wild-type tissue.

PubMed ID
PubMed Central ID
Related Publication(s)
Personal communication to FlyBase

Molecular characterization of Vps25[A3].
Vaccari, 2013.11.5, Molecular characterization of Vps25[A3]. [FBrf0223206]

Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Dev. Cell
    Title
    Developmental Cell
    Publication Year
    2001-
    ISBN/ISSN
    1534-5807 1878-1551
    Data From Reference
    Aberrations (1)
    Alleles (11)
    Genes (10)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (3)
    Transgenic Constructs (5)