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Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response.

Conn KL, Wasson P, McFarlane S, Tong L, Brown JR, Grant KG, Domingues P, Boutell C - J. Virol. (2016)

Bottom Line: Despite characterization of the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that mediate these SUMOylation events remain to be defined.Moreover, in the absence of ICP0, high-molecular-weight SUMO-conjugated proteins do not accumulate if HSV-1 DNA does not replicate.The protein inhibitor of activated STAT (PIAS) family of SUMO ligases is predominantly associated with the suppression of innate immune signaling.

View Article: PubMed Central - PubMed

Affiliation: MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow, Scotland, United Kingdom.

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PIAS4 relocalizes to PML-NBs in a SIM- or ligase-dependent manner in the absence of SAP- or LxxLL-mediated interactions. Confocal images show the localization of eYFP or eYFP.PIAS4 wild-type or mutant proteins with respect to PML-NBs after 6 to 8 h of DOX induction. PML-NBs were identified by PML accumulation; PML was visualized by indirect immunofluorescence (red). Nuclei were visualized by DAPI (blue).
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Figure 5: PIAS4 relocalizes to PML-NBs in a SIM- or ligase-dependent manner in the absence of SAP- or LxxLL-mediated interactions. Confocal images show the localization of eYFP or eYFP.PIAS4 wild-type or mutant proteins with respect to PML-NBs after 6 to 8 h of DOX induction. PML-NBs were identified by PML accumulation; PML was visualized by indirect immunofluorescence (red). Nuclei were visualized by DAPI (blue).

Mentions: Amino-terminal fusion of eYFP did not adversely affect PIAS4 subnuclear localization (Fig. 5B). Inactivation of PIAS4 SUMO ligase activity (C342A), deletion of the SAP domain, or mutation of the LxxLL motif or SIM disrupted PIAS4 MAR localization (Fig. 5C to E and G). In contrast to the catalytically inactive or SIM mutant proteins, however, the ΔSAP and mLxxLL mutants localized to PML-NBs (Fig. 5D and E). Mutation of the PINIT motif resulted in an intermediate phenotype, with subpopulations of PIAS4 localized at PML-NBs or nuclear diffuse (Fig. 5F), suggesting that this motif stabilizes either localization. Deletion of the C-terminal AD (ΔC34) caused a nuclear diffuse and cytoplasmic localization, implicating this domain in nuclear retention or transport of PIAS4 (Fig. 5I).


Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response.

Conn KL, Wasson P, McFarlane S, Tong L, Brown JR, Grant KG, Domingues P, Boutell C - J. Virol. (2016)

PIAS4 relocalizes to PML-NBs in a SIM- or ligase-dependent manner in the absence of SAP- or LxxLL-mediated interactions. Confocal images show the localization of eYFP or eYFP.PIAS4 wild-type or mutant proteins with respect to PML-NBs after 6 to 8 h of DOX induction. PML-NBs were identified by PML accumulation; PML was visualized by indirect immunofluorescence (red). Nuclei were visualized by DAPI (blue).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836348&req=5

Figure 5: PIAS4 relocalizes to PML-NBs in a SIM- or ligase-dependent manner in the absence of SAP- or LxxLL-mediated interactions. Confocal images show the localization of eYFP or eYFP.PIAS4 wild-type or mutant proteins with respect to PML-NBs after 6 to 8 h of DOX induction. PML-NBs were identified by PML accumulation; PML was visualized by indirect immunofluorescence (red). Nuclei were visualized by DAPI (blue).
Mentions: Amino-terminal fusion of eYFP did not adversely affect PIAS4 subnuclear localization (Fig. 5B). Inactivation of PIAS4 SUMO ligase activity (C342A), deletion of the SAP domain, or mutation of the LxxLL motif or SIM disrupted PIAS4 MAR localization (Fig. 5C to E and G). In contrast to the catalytically inactive or SIM mutant proteins, however, the ΔSAP and mLxxLL mutants localized to PML-NBs (Fig. 5D and E). Mutation of the PINIT motif resulted in an intermediate phenotype, with subpopulations of PIAS4 localized at PML-NBs or nuclear diffuse (Fig. 5F), suggesting that this motif stabilizes either localization. Deletion of the C-terminal AD (ΔC34) caused a nuclear diffuse and cytoplasmic localization, implicating this domain in nuclear retention or transport of PIAS4 (Fig. 5I).

Bottom Line: Despite characterization of the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that mediate these SUMOylation events remain to be defined.Moreover, in the absence of ICP0, high-molecular-weight SUMO-conjugated proteins do not accumulate if HSV-1 DNA does not replicate.The protein inhibitor of activated STAT (PIAS) family of SUMO ligases is predominantly associated with the suppression of innate immune signaling.

View Article: PubMed Central - PubMed

Affiliation: MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow, Scotland, United Kingdom.

Show MeSH
Related in: MedlinePlus