Intracellular localization of GASP/ECOP/VOPP1

Alexander Baras, Christopher A. Moskaluk

Research output: Contribution to journalArticle

Abstract

Vesicular Over-expressed in cancer Prosurvival Protein 1 (VOPP1), also known as Glioblastoma Amplified and Secreted Protein and EGFR-Coamplified and Over-expressed Protein has been previously shown to be over-expressed in human glioblastoma multiforme and squamous cell carcinoma. Additionally, previous experimental work suggests that it confers a prosurvival cellular phenotype. A query of a public database of gene expression profiling data (Oncomine™) shows that the VOPP1 transcript is also highly expressed in several other common human cancers, including breast carcinoma, pancreatic carcinoma, and lymphoma. Analysis of VOPP1 sequence structure shows both a signal sequence and a transmembrane domain, and examination of a public microarray dataset for endoplasmic reticulum (ER)-bound mRNA transcripts is consistent with the VOPP1 protein product being synthesized into the ER. Immunoblot analysis of cell culture and conditioned media confirms that the protein product is not secreted and is retained intracellularly. VOPP1 protein tagged with a fluorescence reporter, as well as antibody-mediated visualization of recombinant and native forms of the protein reveals an intracellular vesicular pattern of localization. Co-localization experiments reveal that VOPP1 vesicles do not co-localize with mitochondria or peroxisomes, but show partial co-localization with perinuclear lysosomes. Additionally, markers of endocytosis and autophagy show partial perinuclear co-localization, suggesting that VOPP1-containing vesicles enter final common pathways of the lysosomal system. These findings throw into doubt the hypothesis that VOPP1 interacts directly with cytoplasmic mediators of the NF kappa B pathway, and suggest that the prosurvival phenotype conferred by this gene product is mediated by other mechanisms.

Original languageEnglish (US)
Pages (from-to)153-164
Number of pages12
JournalJournal of Molecular Histology
Volume41
Issue number2-3
DOIs
StatePublished - Apr 2010
Externally publishedYes

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Neoplasms
Proteins
Glioblastoma
Endoplasmic Reticulum
Breast Neoplasms
Phenotype
Peroxisomes
NF-kappa B
Autophagy
Gene Expression Profiling
Conditioned Culture Medium
Protein Sorting Signals
Endocytosis
Lysosomes
Culture Media
Squamous Cell Carcinoma
Lymphoma
Mitochondria
Cell Culture Techniques
Fluorescence

Keywords

  • ECOP
  • GASP
  • Lysosome
  • Vesicle
  • VOPP1

ASJC Scopus subject areas

  • Cell Biology
  • Physiology
  • Histology

Cite this

Intracellular localization of GASP/ECOP/VOPP1. / Baras, Alexander; Moskaluk, Christopher A.

In: Journal of Molecular Histology, Vol. 41, No. 2-3, 04.2010, p. 153-164.

Research output: Contribution to journalArticle

Baras, Alexander ; Moskaluk, Christopher A. / Intracellular localization of GASP/ECOP/VOPP1. In: Journal of Molecular Histology. 2010 ; Vol. 41, No. 2-3. pp. 153-164.
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