Poliovirus 2A protease induces apoptotic cell death.
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.
Goldstaub
D
D
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Gradi
A
A
Bercovitch
Z
Z
Grosmann
Z
Z
Nophar
Y
Y
Luria
S
S
Sonenberg
N
N
Kahana
C
C
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000502:physiology*; D004790:Enzyme Induction; D039603:Eukaryotic Initiation Factor-4G; D015870:Gene Expression; D006801:Humans; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism; D017955:Poliovirus / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins
D039603:Eukaryotic Initiation Factor-4G; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; C057400:picornain 2A, Picornavirus