Ultrastructural localization of BHRF1: an Epstein-Barr virus gene product which has homology with bcl-2.
BHRF1 is an Epstein-Barr virus encoded protein which has a 38% sequence similarity with bcl-2 over the carboxyl portion. Like bcl-2, BHRF1 has been shown to suppress programmed cell death from apoptosis. Previously BHRF1 has been detected in mitochondrial, microsomal, and nuclear compartments by cell fractionation analysis. In this study we have used the technique of immunoelectron microscopy to define the ultrastructural distribution of the BHRF1 product in the EBV converted cell lines B95.8 and P3HR-1. The BHRF1 product was localized at the periphery of the mitochondria in a pattern similar to that of bcl-2 and by analogy with bcl-2 this is likely to be the functional destination. Sequence analysis of the BHRF1 protein disclosed similarity with the recently described bcl-2 homologues bcl-x (32%) and bax (34%) over the carboxyl portion, with several domains of complete identity. BHRF1 appears to be a member of a gene family involved in the regulation of programmed cell death. The identity between BHRF1 and bcl-2, an apparent shared ability to abrogate apoptosis, and the common ultrastructural localization is compelling and suggests that bcl-2 and BHRF1 are both functionally and mechanistically similar.
Hickish
T
T
Lymphoma Unit, Royal Marsden Hospital, Sutton, Surrey, United Kingdom.
Robertson
D
D
Clarke
P
P
Hill
M
M
di Stefano
F
F
Clarke
C
C
Cunningham
D
D
D000595:Amino Acid Sequence; D000818:Animals; D002144:Callithrix; D002460:Cell Line; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000737:chemistry*; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins / Q000032:analysis*
C083278:BHRF1 protein, Human herpesvirus 4; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins