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Molecular and Cellular Biology, February 2000, p. 1271-1277, Vol. 20, No. 4
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Poliovirus 2A Protease Induces Apoptotic Cell Death

Dan Goldstaub,1 Alessandra Gradi,2 Zippi Bercovitch,1 Zehava Grosmann,3,dagger Yaron Nophar,3 Sylvie Luria,3 Nahum Sonenberg,2 and Chaim Kahana1,*

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100,1 and QBI Enterprises, Nes Ziona 74106,3 Israel, and Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada2

Received 10 August 1999/Returned for modification 25 October 1999/Accepted 9 November 1999

A cell line was generated that expresses the poliovirus 2A protease in an inducible manner. Tightly controlled expression was achieved by utilizing the muristerone A-regulated expression system. Upon induction, cleavage of the eukaryotic translation initiation factor 4GI (eIF4GI) and eIF4GII is observed, with the latter being cleaved in a somewhat slower kinetics. eIF4G cleavage was accompanied by a severe inhibition of protein synthesis activity. Upon induction of the poliovirus 2A protease, the cells displayed fragmented nuclei, chromatin condensation, oligonucleosome-size DNA ladder, and positive TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) staining; hence, their death can be characterized as apoptosis. These results indicate that the expression of the 2A protease in mammalian cells is sufficient to induce apoptosis. We suggest that the poliovirus 2A protease induces apoptosis either by arresting cap-dependent translation of some cellular mRNAs that encode proteins required for cell viability, by preferential cap-independent translation of cellular mRNAs encoding apoptosis inducing proteins, or by cleaving other, yet unidentified cellular target proteins.

* Corresponding author. Mailing address: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel. Phone: 972-8-9342745. Fax: 972-8-9466599 or 972-8-9344108. E-mail: lvkahana{at}weizmann.weizmann.ac.il.

dagger Present address: Central Virology Laboratory, Sheba Medical Center, Tel-Hashomer 52621, Israel.

Molecular and Cellular Biology, February 2000, p. 1271-1277, Vol. 20, No. 4
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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