The Baculovirus PE38 Protein Augments Apoptosis Induced by Transactivator IE1

Abstract

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.

Nuclear localization of actin requires AC102 in Autographa californica multiple nucleopolyhedrovirus-infected cells

“…For example, PE38 could ubiquitinate the actin-specific nuclear export protein exportin-6, ultimately facilitating the nuclear accumulation of actin (Stüven et al, 2003). Another possibility involves PE38's role in enhancing IE1-induced apoptosis (Prikhod'ko & Miller, 1999), a stress that could lead to the accumulation of actin within the nucleus (Luchetti et al, 2002), even though apoptosis is ultimately blocked (Clem, 2007).…”

“…Of these, only HE65 and PE38 have been characterized previously. Functions ascribed to PE38 include acting as an early gene transactivator, a ubiquitin ligase, a factor in DNA replication and an enhancer of IE1-induced apoptosis (Imai et al, 2003;Kool et al, 1994;Lu & Carstens, 1993;Prikhod'ko & Miller, 1999). HE65 is an early gene product with similarity to the RNA ligase 2 nt binding pocket, but RNA ligase activity has not been confirmed experimentally (Becker & Knebel-Mörsdorf, 1993;Ho & Shuman, 2002).…”

A natural point mutation changes both target selectivity and mechanism of action of sea anemone toxins

“…The insect-specificity of APETx3 is demonstrated by the complete inhibition of the inactivation of the insect Na V channels DmNa V 1 and BgNa V 1.1, and it is furthermore emphasized by the 10-fold difference in EC 50 values between mammalian (Na V 1.6) and insect (DmNa V 1) channels. This preference for insect Na V channels suggests that APETx3 can be used as an insecticide (34,35).…”

Induction of apoptosis in an insect cell line, IPLB-Ld652Y, infected with nucleopolyhedroviruses

“…Previous studies have also shown that AcMNPV-induced apoptosis of Sf21 cells is triggered by IE1, the product of the immediateearly viral gene ie1 (Prikhod'ko & Miller, 1996), and suppressed by P35 and inhibitor of apoptosis (IAP) proteins, which are encoded by the genomes of certain NPVs (Clem, 1997(Clem, , 2001). It has also been shown that IE1-induced apoptosis of Sf21 cells is augmented by the AcMNPV early gene product PE38 (Prikhod'ko & Miller, 1999). In addition, apoptosis induced by baculovirus infection has been shown to be associated with the activation of caspases (Bertin et al, 1996;Ahmad et al, 1997;LaCount & Friesen, 1997;Seshagiri & Miller, 1997;LaCount et al, 2000;Manji & Friesen, 2001).…”