Involvement of branched-chain amino acid aminotransferase (Bcat1/Eca39) in apoptosis.

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Eden A,Benvenisty N

doi

10.1016/s0014-5793(99)01054-6

keywords:

subject

Has Abstract

pub_date

1999-08-27 00:00:00

pages

255-61

issue

2

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(99)01054-6

journal_volume

457

pub_type

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