Identification of the Role of MnSOD in EGFR-Positive Breast Cancer Development

Abstract

HSpry2 has been identified as a modulator of RTK signaling pathways, and growth factor stimulation regulates hSpry2 expression and function establishing complex regulatory network. We are interested in identifying factors that control the biological activity of hSpry2. Previously our lab has shown that growth factor stimulation induces the proteasomal degradation of hSpry2 through poly-ubiquitination by E3 ubiquitin ligase, c-Cbl. Recently we found that hSpry2 is also mono-ubiquitinated. In order to characterize the function of hSpry2 mono-ubiquitination, we generated an hSpry2 ubiquitination-deficient mutant by site directed mutagenesis. Indirect immunofluorescent microscopy showed that hSpry2 ubiquitination-deficient mutant localizes to Golgi apparatus whereas wild- type hSpry2 localizes to both the Golgi and the cytoplasmic vesicular structures. Cytoplasmic vesicular localization of the mutant was regained by fusing a single ubiqutin molecule to it, strongly suggesting the involvement of mono-ubiquitination in intracellular trafficking. Taken together, these results indicate that hSpry2 monoubiquitination serves as a signal for its Golgi to endosome trafficking.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2004
Accession Number
ADA427130

Entities

People

  • Dafna Bar-sagi
  • Hong J. Kim

Organizations

  • State University of New York

Tags

DTIC Thesaurus Topics

  • Biological Sciences
  • Blood
  • Cell Membrane
  • Cell Movement
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Chemistry
  • Cytoplasmic Structures
  • Endothelial Cells
  • Genetics
  • Growth Factors
  • Molecules
  • Peptide Growth Factors
  • Peptides
  • Proteins

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular Genetics