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REPORT DATE (DD-MM-YYYY)
01-05-2006
REPORT TYPE
Annual Summary
DATES COVERED
PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERUniversity of Arkansas Little Rock, Arkansas 72205
SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)
U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012
SPONSOR/MONITOR'S REPORT NUMBER(S)
DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited
SUPPLEMENTARY NOTES
ABSTRACTThe conserved oligomeric Golgi (COG) complex consists of eight subunits that are thought to be involved in vesicle tethering. Available mutants with the mutations in COG complex subunits exhibit defects in basic Golgi functions: protein glycosylation and its sorting. For analysis of COG complex function we utilized RNA interference assay to knockdown COG3p subunit of COG complex in normal and breast cancer cells and other tumor cell lines. Acute knockdown of the COG3 was accompanied by reduction in Cog1, 2 and 4 protein levels, rapid Golgi fragmentation and accumulation of COG complex dependent (CCD) vesicles. Constantly cycling medial-Golgi enzymes are transported from distal compartments in CCD vesicles. Dysfunction of COG complex leads to separation of glycosyltransferases from anterograde cargo molecules passing along secretory pathway, thus affecting normal protein glycosylation. Altered level of COG3p (or COG complex) expression could be a common feature of cancer cells defective in protein trafficking and Golgi modifications. The importance of the COG complex for both function and architecture of the Golgi apparatus does not depend on cell type. Partial malfunction of the COG complex may play a role in establishing of cancer phenotype.
SUBJECT TERMS
IntroductionIn breast, colon and skin cancers, the unusual production and secretion of aberrantly glycosylated proteins and lipids on the surface are associated with disease progression, metastasis and poor clinical outcome (1). Glycosylation abnormalities concern both N-linked and O-linked carbohyd...