K1 protein of human herpesvirus 8 suppresses lymphoma cell Fas-mediated apoptosis.
Expression of the K1 gene of human herpesvirus 8 activates nuclear factor-kappaB 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.
Wang
Suizhao
S
Department of Lymphoma and Myeloma, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Wang
Shu
S
Maeng
Hoyoung
H
Young
Daniel P
DP
Prakash
Om
O
Fayad
Luis E
LE
Younes
Anas
A
Samaniego
Felipe
F
D000906:Antibodies / Q000276:immunology; D017209:Apoptosis; D045744:Cell Line, Tumor; D015870:Gene Expression; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010957:Plasmids / Q000235:genetics; D015996:Survival Rate; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; C111600:K1 protein, Human herpesvirus 8; D014764:Viral Proteins; D019014:fas Receptor