Involvement of branched-chain amino acid aminotransferase (Bcat1/Eca39) in apoptosis.
The branched-chain amino acid aminotransferase, Bcat1/Eca39, catalyzes the first step of branched-chain amino acid catabolism. Bcat1/Eca39 was originally isolated from a c-myc-induced tumor and was proven to be a direct target for c-Myc regulation. The gene is highly conserved in evolution and disruption of its yeast homolog affects cell growth. To assess the role of Bcat1/Eca39 in mammalian cells, we overexpressed Bcat1/Eca39 in murine cells and studied effects on cell growth. Overexpression of Bcat1/Eca39 had no apparent effect on the proliferation of cells grown with high serum concentrations, but under serum deprivation conditions, led to a decrease in cell viability. Cell death under these conditions displayed apoptotic features. The branched-chain keto acid, alpha-ketoisocaproate, a metabolite of leucine catabolism produced by BCAT1/ECA39, was previously found to inhibit cell growth. We show that alpha-ketoisocaproate can induce rapid apoptotic cell death. This observation suggests that the growth inhibitory effect of BCAT1/ECA39 and its apoptosis promoting effect may be mediated by the levels of the products of BCAT1/ECA39 activity, namely, branched-chain keto acids.
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Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Givat-Ram, Jerusalem, Israel.
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D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D007651:Keto Acids / Q000494:pharmacology; D051379:Mice; D010957:Plasmids / Q000235:genetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000502:physiology*; D000637:Transaminases
D007651:Keto Acids; D011506:Proteins; C013082:alpha-ketoisocaproic acid; C094227:Bcat1 protein, mouse; D000637:Transaminases