The baculovirus PE38 protein augments apoptosis induced by transactivator IE1.
While studying apoptosis induced by baculovirus transactivator IE1 in SF-21 cells, we found that the levels of IE1-induced apoptosis were increased approximately twofold upon cotransfection with the baculovirus early pe38 gene. However, no apoptotic activity was observed in cells transfected with pe38 alone, even when placed under the control of a constitutive promoter. Thus, pe38 was able to augment IE1-induced apoptosis but was unable to induce apoptosis when expressed in SF-21 cells alone. PE38, the full-length product of pe38, is a nuclear protein with RING finger and leucine zipper motifs. Deletion of the amino-terminal region, which contains a putative nuclear localization motif, resulted in cytoplasmic localization of the PE38 mutants. These N-terminal deletion mutants were unable to enhance IE1-induced apoptosis. Mutation of a single conserved leucine (L242) of the leucine zipper motif also eliminated the ability of PE38 to augment apoptosis induced by IE1. In contrast, PE38 mutants with alanine substitutions for conserved cysteine residues (C109 or C138) of the RING finger motif were able to increase IE1-induced apoptosis to levels equivalent to those of wild-type PE38. We propose that PE38 is one of at least two viral factors which collectively evoke a cellular apoptotic response during baculovirus infection.
Departments of Entomology and Genetics, The University of Georgia, Athens, Georgia 30602, USA.
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Prikhod'ko
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Miller
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D016296:Mutagenesis; D018411:Spodoptera / Q000166:cytology; D013347:Subcellular Fractions; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins; D016335:Zinc Fingers
C069183:Ac-IE-1 protein, Autographa californica nucleopolyhedrovirus; C095109:Ac-PE38 protein, Autographa californica nucleopolyhedrovirus; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D014764:Viral Proteins