Adenovirus E3-6.7K maintains calcium homeostasis and prevents apoptosis and arachidonic acid release.
E3-6.7K is a small and hydrophobic membrane glycoprotein encoded by the E3 region of subgroup C adenovirus. Recently, E3-6.7K has been shown to be required for the downregulation of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors by the adenovirus E3/10.4K and E3/14.5K complex of proteins. We demonstrate here that E3-6.7K has additional protective roles, independent of other virus proteins. In transfected Jurkat T-cell lymphoma cells, E3-6.7K was found to maintain endoplasmic reticulum-Ca(2+) homeostasis and inhibit the induction of apoptosis by thapsigargin. The presence of E3-6.7K also lead to a reduction in the TNF-induced release of arachidonic acid from transfected U937 human histiocytic lymphoma cells. In addition, E3-6.7K protected cells against apoptosis induced through Fas, TNF receptor, and TRAIL receptors. Therefore, E3-6.7K confers a wide range of protective effects against both Ca(2+) flux-induced and death receptor-mediated apoptosis.
Moise
Alexander R
AR
Biotechnology Laboratory, Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Grant
Jason R
JR
Vitalis
Timothy Z
TZ
Jefferies
Wilfred A
WA
D017503:Adenovirus E3 Proteins / Q000235:genetics / Q000494:pharmacology*; D000260:Adenoviruses, Human / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D016718:Arachidonic Acid / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection
D017503:Adenovirus E3 Proteins; C087149:E3-6.7K protein, Adenovirus; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D016718:Arachidonic Acid; D019284:Thapsigargin; D002118:Calcium