Yeast Eap1p, an elF4E-associated protein, has a separate function involving genetic stability

Heidi J. Chial, Alexander J. Stemm-Wolf, Susan McBratney, Mark Winey

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

A rate-limiting step during translation initiation in eukaryotic cells involves binding of the initiation factor elF4E to the 7-methylguanosine-containing cap of mRNAs. Overexpression of elF4E leads to malignant transformation [1-3], and elF4E is elevated in many human cancers [4-7]. In mammalian cells, three elF4E-binding proteins each interact with elF4E and inhibit its function [8-10]. In yeast, EAP1 encodes a protein that binds elF4E and inhibits cap-dependent translation in vitro [11]. A point mutation in the canonical elF4E-binding motif of Eaplp blocks its interaction with elF4E [11]. Here, we characterized the genetic interactions between EAP1 and NDC1, a gene whose function is required for duplication of the spindle pole body (SPB) [12], the centrosome-equivalent organelle in yeast that functions as the centrosome. We found that the deletion of EAP1 is lethal when combined with the ndc1-1 mutation. Mutations in NDC1 or altered NDC1 gene dosage lead to genetic instability [13,14]. Yeast strains lacking EAP1 also exhibit genetic instability. We tested whether these phenotypes are due to loss of EAP1 function in regulating translation. We found that both the synthetic lethal phenotype and the genetic instability phenotypes are rescued by a mutant allele of EAP1 that is unable to bind elF4E. Our findings suggest that Ea p1p carries out an elF4E-independent function to maintain genetic stability, most likely involving SPBs.

Original languageEnglish (US)
Pages (from-to)1519-1522
Number of pages4
JournalCurrent Biology
Volume10
Issue number23
DOIs
StatePublished - Nov 30 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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