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Journal of Virology, February 2002, p. 1578-1587, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1578-1587.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Adenovirus E3-6.7K Maintains Calcium Homeostasis and Prevents Apoptosis and Arachidonic Acid Release

Alexander R. Moise,1,2 Jason R. Grant,1,2 Timothy Z. Vitalis,3 and Wilfred A. Jefferies1,2*

Biotechnology Laboratory,,1 Biomedical Research Centre, and Departments of Medical Genetics, Microbiology and Immunology, and Zoology, University of British Columbia, Vancouver, British Columbia V6T 1Z3,,2 Pulmonary Research Laboratory, University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia V6Z 1Y6, Canada3

Received 5 June 2001/ Accepted 9 November 2001

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-Ca2+ 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 Ca2+ flux-induced and death receptor-mediated apoptosis.

* Corresponding author. Mailing address: The Biomedical Research Centre, 2222 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Phone: (604) 822-6961. Fax: (604) 822-6780. E-mail: wilf{at}unixg.ubc.ca.

Journal of Virology, February 2002, p. 1578-1587, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1578-1587.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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