Involvement of branched‐chain amino acid aminotransferase ( Bcat1 / Eca39 ) in apoptosis
1999; Wiley; Volume: 457; Issue: 2 Linguagem: Inglês
10.1016/s0014-5793(99)01054-6
ISSN1873-3468
Autores Tópico(s)Protein Degradation and Inhibitors
ResumoThe 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, α‐ketoisocaproate, a metabolite of leucine catabolism produced by BCAT1/ECA39, was previously found to inhibit cell growth. We show that α‐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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