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Molecular and Cellular Biology, July 2000, p. 4604-4613, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Eap1p, a Novel Eukaryotic Translation Initiation Factor 4E-Associated Protein in Saccharomyces cerevisiae

Gregory P. Cosentino,1,2 Tobias Schmelzle,3 Ashkan Haghighat,1,dagger Stephen B. Helliwell,3,Dagger Michael N. Hall,3 and Nahum Sonenberg1,*

Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Québec H3G 1Y6,1 and Bio-Méga Research Division, Boehringer Ingelheim (Canada) Ltd., Laval, Québec, H7S 2G5,2 Canada, and Department of Biochemistry, Biozentrum, University of Basel, CH-4056, Basel, Switzerland3

Received 12 July 1999/Returned for modification 2 September 1999/Accepted 27 March 2000

Ribosome binding to eukaryotic mRNA is a multistep process which is mediated by the cap structure [m7G(5')ppp(5')N, where N is any nucleotide] present at the 5' termini of all cellular (with the exception of organellar) mRNAs. The heterotrimeric complex, eukaryotic initiation factor 4F (eIF4F), interacts directly with the cap structure via the eIF4E subunit and functions to assemble a ribosomal initiation complex on the mRNA. In mammalian cells, eIF4E activity is regulated in part by three related translational repressors (4E-BPs), which bind to eIF4E directly and preclude the assembly of eIF4F. No structural counterpart to 4E-BPs exists in the budding yeast, Saccharomyces cerevisiae. However, a functional homolog (named p20) has been described which blocks cap-dependent translation by a mechanism analogous to that of 4E-BPs. We report here on the characterization of a novel yeast eIF4E-associated protein (Eap1p) which can also regulate translation through binding to eIF4E. Eap1p shares limited homology to p20 in a region which contains the canonical eIF4E-binding motif. Deletion of this domain or point mutation abolishes the interaction of Eap1p with eIF4E. Eap1p competes with eIF4G (the large subunit of the cap-binding complex, eIF4F) and p20 for binding to eIF4E in vivo and inhibits cap-dependent translation in vitro. Targeted disruption of the EAP1 gene results in a temperature-sensitive phenotype and also confers partial resistance to growth inhibition by rapamycin. These data indicate that Eap1p plays a role in cell growth and implicates this protein in the TOR signaling cascade of S. cerevisiae.

* Corresponding author. Mailing address: Department of Biochemistry, McGill University, 3655 Drummond St., Rm. 807, Montreal, Québec H3G 1Y6, Canada. Phone: (514) 398-7274. Fax: (514) 398-1287. E-mail: nsonen{at}med.mcgill.ca.

dagger Present address: Caprion Pharmaceuticals Inc., Montreal, Québec, H4P 2R2, Canada.

Dagger Present address: Department of Biology, Massachusetts Institute of Technology, Cambridge MA 02139-4307.

Molecular and Cellular Biology, July 2000, p. 4604-4613, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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