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

Amir Eden; Nissim Benvenisty

doi:10.1016/S0014-5793(99)01054-6

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

Amir Eden
, Nissim Benvenisty^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

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, 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. Copyright (C) 1999 Federation of European Biochemical Societies.

Original language	English
Pages (from-to)	255-261
Number of pages	7
Journal	FEBS Letters
Volume	457
Issue number	2
DOIs	https://doi.org/10.1016/S0014-5793(99)01054-6
State	Published - 27 Aug 1999

Bibliographical note

Funding Information:
We thank Dr. Shoshana Klein and Ittai Ben-Porath for critical reading of the manuscript and Dr. Ofra Yanuka for technical assistance. This research was supported by grant # 3811a from The Council For Tobacco Research, by grant # 93-00017 from the United States-Israel Binational Science Foundation (BSF), Jerusalem, Israel and by the Huruvitz Fund. FACS analysis was performed using equipment purchased by a grant from the Israel National Foundation.

Keywords

Aminotransferase
Apoptosis
Branched-chain amino acid
Keto acid

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10.1016/S0014-5793(99)01054-6

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title = "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, 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. Copyright (C) 1999 Federation of European Biochemical Societies.",

keywords = "Aminotransferase, Apoptosis, Branched-chain amino acid, Keto acid",

author = "Amir Eden and Nissim Benvenisty",

note = "Funding Information: We thank Dr. Shoshana Klein and Ittai Ben-Porath for critical reading of the manuscript and Dr. Ofra Yanuka for technical assistance. This research was supported by grant \# 3811a from The Council For Tobacco Research, by grant \# 93-00017 from the United States-Israel Binational Science Foundation (BSF), Jerusalem, Israel and by the Huruvitz Fund. FACS analysis was performed using equipment purchased by a grant from the Israel National Foundation. ",

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N2 - 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, 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. Copyright (C) 1999 Federation of European Biochemical Societies.

AB - 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, 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. Copyright (C) 1999 Federation of European Biochemical Societies.

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

Abstract

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Keywords

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