Repression of bax gene expression by the HTLV-1 Tax protein: implications for suppression of apoptosis in virally infected cells.
The human T-cell leukemia virus-encoded oncoprotein Tax is a potent deregulator of cellular gene expression. Here we report that Tax represses transcription of the human bax gene, a gene whose protein product accelerates apoptosis. This repression is mediated through a 27-bp sequence in the bax promoter that contains a putative basic helix-loop-helix binding site. Deletion of this sequence abolishes Tax-mediated repression of bax. Repression of the bax gene may be biologically significant, as we also show that HTLV-I-infected cell lines are resistant to a variety of physical, chemical, and biological stimuli which induce apoptosis in uninfected T-cells. The repression of genes involved in promoting apoptosis, including the bax gene, may contribute to retroviral survival, and initiate a pathway toward malignant transformation.
Brauweiler
A
A
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins 80523-1870, USA.
Garrus
J E
JE
Reed
J C
JC
Nyborg
J K
JK
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000235:genetics / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D016356:Gene Products, tax; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein