A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak

Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):690-4. doi: 10.1073/pnas.94.2.690.


The Bcl-2 protein family is characterized by the ability to modulate cell death, and members of this family share two highly conserved domains called Bcl-2 homology 1 (BH1) and 2 (BH2) which have been shown to be critical for the death-repressor activity of Bcl-2 and Bcl-xL. Through sequence analysis we identified a novel viral Bcl-2 homolog, designated KSbcl-2, from human herpesvirus 8 (HHV8) or Kaposi sarcoma-associated herpesvirus. The overall amino acid sequence identity between KSbcl-2 and other Bcl-2 homologs is low (15-20%) but concentrated within the BH1 and BH2 regions. Overexpression of KSbcl-2 blocked apoptosis as efficiently as Bcl-2, Bcl-xL, or another viral Bcl-2 homolog encoded by Epstein-Barr virus, BHRF1. Interestingly, KS-bcl-2 neither homodimerizes nor heterodimerizes with other Bcl-2 family members, suggesting that KSbcl-2 may have evolved to escape any negative regulatory effects of the cellular Bax and Bak proteins. Furthermore, the herpesvirus Bcl-2 homologs including KSbcl-2, BHRF1, and ORF16 of herpesvirus saimiri contain poorly conserved Bcl-2 homology 3 (BH3) domains compared with other mammalian Bcl-2 homologs, implying that BH3 may not be essential for anti-apoptotic function. This is consistent with our observation that amino acid substitutions within the BH3 domain of Bcl-xL had no effect on its death-suppressor activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Apoptosis
  • Genes, Viral*
  • Herpesvirus 8, Human / genetics*
  • Humans
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Sarcoma, Kaposi / genetics*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sindbis Virus
  • Viral Proteins / metabolism*
  • Viral Structural Proteins / genetics*
  • Virus Replication
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein


  • BAK1 protein, human
  • BAX protein, human
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Viral Proteins
  • Viral Structural Proteins
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein

Associated data

  • GENBANK/U67773