Suppression of c-Myc-induced apoptosis by the Epstein-Barr virus gene product BHRF1.
Constitutive expression of the c-myc proto-oncogene in growth factor-deprived fibroblasts promotes proliferation and induces apoptosis. In these cells, apoptosis can be inhibited by survival factors such as insulin-like growth factor I or the bcl-2 proto-oncogene product. Deregulated c-Myc expression is a common feature in Epstein-Barr virus-positive Burkitt's lymphoma in which the c-myc gene is reciprocally translocated and placed under the control of one of the immunoglobulin loci. BHRF1 is an Epstein-Barr virus protein expressed early in the lytic cycle. BHRF1 is a member of the Bcl-2 family and has been shown to suppress apoptosis and to increase cell survival in different settings. In the present study, we report that BHRF1 inhibits c-Myc-induced apoptosis which occurs in the absence of survival factors. It does not, however, affect the capacity of c-Myc to promote cell growth. These findings demonstrate that BHRF1 has not only structural but also functional similarities to Bcl-2.
Fanidi
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A
Biochemistry of the Cell Nucleus, Imperial Cancer Research Fund Laboratories, London WC2A 3PX, United Kingdom. afanidi@onyx-pharm.com
Hancock
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DC
Littlewood
T D
TD
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D014764:Viral Proteins / Q000378:metabolism*
C083278:BHRF1 protein, Human herpesvirus 4; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D014764:Viral Proteins