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J. Biol. Chem., Vol. 281, Issue 11, 7452-7457, March 17, 2006

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The Essential Vertebrate ABCE1 Protein Interacts with Eukaryotic Initiation Factors^*

Zhang-qun Chen, Jinsheng Dong, Akihiko Ishimura^¶, Ira Daar^¶, Alan G. Hinnebusch, and Michael Dean^||1

From the Basic Research Program, SAIC-Frederick, Inc., NCI, National Institutes of Health, Frederick, Maryland 21702, the Laboratory of Gene Regulation and Development, NICHD, National Institutes of Health, Bethesda, Maryland 20892, the ^¶Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702, and the ^||Laboratory of Genomic Diversity, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 217024

The ABCE1 gene is a member of the ATP-binding cassette (ABC) multigene family and is composed of two nucleotide binding domains and an N-terminal Fe-S binding domain. The ABCE1 gene encodes a protein originally identified for its inhibition of ribonuclease L, a nuclease induced by interferon in mammalian cells. The protein is also required for the assembly of the HIV and SIV gag polypeptides. However, ABCE1 is one of the most highly conserved proteins and is found in one or two copies in all characterized eukaryotes and archaea. Yeast ABCE1/RLI1 is essential to cell division and interacts with translation initiation factors in the assembly of the pre-initiation complex. We show here that the human ABCE1 protein is essential for in vitro and in vivo translation of mRNA and that it binds to eIF2 and eIF5. Inhibition of the Xenopus ABCE1 arrests growth at the gastrula stage of development, consistent with a block in translation. The human ABCE1 gene contains 16 introns, and the extremely high degree of amino acid identity allows the evolution of its introns to be examined throughout eukaryotes. The demonstration that ABCE1 plays a role in vertebrate translation initiation extends the known functions of this highly conserved protein. Translation is a highly regulated process important to development and pathologies such as cancer, making ABCE1 a potential target for therapeutics. The evolutionary analysis supports a model in which an ancestral eukaryote had large number of introns and that many of these introns were lost in non-vertebrate lineages.

Received for publication, September 28, 2005 , and in revised form, January 18, 2006.

^* This work was supported in part with federal funds from the NCI, National Institutes of Health (NIH), under Contract No. NO1CO-12400 and by the Intramural Research Program of the NIH, NCI, Center for Cancer Research, and NICHD. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S3.

¹ To whom correspondence should be addressed. Tel.: 301-846-5931; Fax: 301-846-1909; E-mail: dean{at}ncifcrf.gov.

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