|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
Blood, 1 March 2007, Vol. 109, No. 5, pp. 2174-2182. Prepublished online as a Blood First Edition Paper on November 7, 2006; DOI 10.1182/blood-2006-02-003178.
NEOPLASIA K1 protein of human herpesvirus 8 suppresses lymphoma cell Fas-mediated apoptosis1 Departments of Lymphoma and Myeloma and Immunology, The University of Texas M. D. Anderson Cancer Center, Houston; 2 Laboratory of Molecular Oncology and Department of Pathology, Ochsner Clinic Foundation, New Orleans, LA; 3 Graduate Program in Virology and Gene Therapy, The University of Texas Graduate School of Biomedical Sciences at Houston;
Expression of the K1 gene of human herpesvirus 8 activates nuclear factor-
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|||||||||
 |
 |
 |
 |
 |
 |
 |
 |
||||
| |||||||||||
| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||||
B and induces lymph node hyperplasia and lymphomas in transgenic mice. To further delineate its role in cell survival, we determined whether K1 altered apoptosis of lymphoma cells. K1 protein is expressed in Kaposi sarcoma and primary effusion lymphoma. We retrovirally transfected BJAB lymphoma, THP-1, U937, and Kaposi sarcoma SLK cells to express K1 and a K1 mutant with the deleted immunoreceptor tyrosine-based activation motif (K1m). We challenged cells with an agonistic anti-Fas antibody, Fas ligand, irradiation, and tumor necrosis factor–related apoptosis-inducing ligand. K1 transfectants but not K1m transfectants exhibited reduced levels of apoptosis induced by the anti-Fas antibody but not apoptosis induced by the tumor necrosis factor–related apoptosis-inducing ligand or irradiation. K1 expression resulted in reduced apoptosis rates as shown in several assays. K1 induced a modest reduction in levels of Fas-associated death domain protein, and procaspase 8 recruited to the death-inducing signaling complex. Finally, K1 transfectants cleaved procaspase 8 at significantly lower rates than did K1m transfectants. K1-transfected mice, compared with vector-transfected mice, showed lower death rates after challenge with anti-Fas antibody. K1 may contribute to lymphoma development by stimulating cell survival by selectively blocking Fas-mediated apoptosis. 