Inhibition of apoptosis by the African swine fever virus Bcl-2 homologue: role of the BH1 domain.
The function of the African swine fever virus (ASFV) bcl-2 homologue, gene A179L, in the regulation of apoptosis was investigated using as a model system the human myeloid leukemia cell line K562 induced to die by apoptosis with inhibitors of macromolecular synthesis, a process that is prevented by overexpression of human bcl-2. It is shown that transfection of K562 cells with the ASFV A179L gene protects these cells from apoptotic cell death induced by a combination of cycloheximide and actinomycin D or by treatment with cytosine arabinoside. To test the functional role of the highly conserved BH1 domain present in the A179L protein, the Gly residue at position 85 was mutated to Ala, since it has been shown that substitution of the corresponding Gly in human Bcl-2 abrogates its death-repressor activity. It was found that the Gly-to-Ala mutation in the BH1 domain of the viral protein abolished its capacity to protect the K562 cells from apoptosis, indicating that this Gly is essential for A179L action. This finding stresses the functional similarity of the BH1 domains of the viral protein and cellular Bcl-2.
Revilla
Y
Y
Centro de Biologíe Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma, Madrid, Spain.
Cebrián
A
A
Baixerás
E
E
Martínez
C
C
Viñuela
E
E
Salas
M L
ML
D000358:African Swine Fever Virus / Q000235:genetics / Q000502:physiology*; D000409:Alanine; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D003513:Cycloheximide / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005998:Glycine; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000502:physiology; D011817:Rabbits; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins; D003561:Cytarabine; D003609:Dactinomycin; D003513:Cycloheximide; D000409:Alanine; D005998:Glycine