Differential Control of ErbB2 Surface Expression in Breast Cancer Cells by an Alternatively Spliced Form of ERBIN

Abstract

The ErbB2 receptor is upregulated in approximately 30% of early stage breast cancers. Persistent signaling by the receptor induces a mitogenic response in which cells continuously grow and proliferate regardless of environmental conditions. Following ligand binding and receptor activation, many cell surface receptors enter the Multivesicular Body pathway, where they are sorted and either targeted for degradation or recycled back to the plasma membrane. The specific protein-protein interactions of this - pathway, and the mechanism by which sorting occurs, however, are not yet fully understood. Elucidation of the natural mechanism of ErbB2 downregulation could provide insight into the treatments and therapies given to many breast cancer patients. Here, we show that hVps2O and hSnf7, two previously undescribed proteins, are components of the network and are affect cargo within the network. In addition, we also show that Alpi, a previously identified protein for its role in HIV budding, is an active participant to sorting of MVB cargo. Specifically, we show that the N-terminus of AIPi interacts with hSnf7. Further, we show that hSnf7 can disrupt cholesterol trafficking. We continue to contribute to work done by other groups to identify and characterize the mechanism of protein trafficking.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2004
Accession Number
ADA427073

Entities

People

  • Kathryn Ching

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Apoptosis
  • Biomedical And Dental Materials
  • Breast Cancer
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Chemistry
  • Cholesterol
  • Cytoplasmic Vesicles
  • Materials
  • Membranes
  • Molecular Biology
  • Neoplasms
  • Protein-Protein Interactions
  • Proteins

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular and Cellular Biochemistry