Promyelocytic Leukemia Protein (PML) Requirement for Interferon-induced Global Cellular SUMOylation

Maroui, Mohamed Ali; Maarifi, Ghizlane; McManus, Francis P.; Lamoliatte, Frederic; Thibault, Pierre; Chelbi-Alix, Mounira K.

doi:10.1074/mcp.ra117.000447

Cited by 27 publications

(49 citation statements)

References 44 publications

(37 reference statements)

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“…Depletion of PIAS1 and PIAS4 in combination with PML significantly alleviates the restriction of an HSV-1 ΔICP0 mutant relative to PML depletion alone ( Conn et al, 2016 ; Brown et al, 2016 ). Thus, ICP0’s ability to disrupt SUMO-SIM interactions through multiple targeting mechanisms is likely to be a common strategy employed by ICP0 to remodel proteome interaction networks that facilitate or maintain the intracellular restriction of HSV-1 ( Everett and Murray, 2005 ; Cuchet-Lourenco et al, 2011 ; Maroui et al, 2018 ).…”

Section: Icp0-mediated Degradation Of Pml-nbs and Sumoylated Host Promentioning

confidence: 99%

The HSV-1 ubiquitin ligase ICP0: Modifying the cellular proteome to promote infection

et al. 2020

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Highlights ICP0 is a viral E3 ubiquitin ligase that promotes HSV-1 infection. ICP0 interacts with multiple component proteins of the ubiquitin pathway. ICP0 disrupts multiple cellular processes activated in response to infection ICP0 remodels the SUMO proteome to counteract host immune defences to infection. ICP0 is an attractive drug target for the development of antiviral HSV-1 therapeutics.

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Section: Icp0-mediated Degradation Of Pml-nbs and Sumoylated Host Promentioning

confidence: 99%

The HSV-1 ubiquitin ligase ICP0: Modifying the cellular proteome to promote infection

et al. 2020

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“…PML is actually not a single protein but a mixture of seven different isoforms, whereby the first six isoforms (I to VI) are nuclear proteins (51). To determine if IE1 preferentially colocalizes with certain PML isoforms, we co-transfected PML negative (PML -/- ) cells with individual expression plasmids for the six nuclear PML isoforms and IE1 expression vectors.…”

Section: Resultsmentioning

confidence: 99%

Role of PML-Nuclear Bodies in Human Herpesvirus 6A and 6B Genome Integration

Collin

Gravel

Kaufer

et al. 2018

Preprint

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18 Human herpesviruses 6A and 6B (HHV-6A/B) are two betaherpesviruses that readily 19 integrate their genomes into the telomeres of human chromosomes. To date, the cellular 20 or viral proteins that facilitate HHV-6A/B integration remain elusive. In the present study, 21 we demonstrate that the immediate early protein 1 (IE1) of HHV-6A/B colocalizes with 22 telomeres during infection. Moreover, IE1 associates with PML-NBs, a nuclear complex 23 that regulates multiples cellular mechanism including DNA repair and antiviral responses.24 Furthermore, we could demonstrate that IE1 targets all PML isoforms and that both 25 proteins colocalize at telomeres. To determine the role of PML in HHV-6A/B integration, 26 we generated PML knockout cell lines using CRISPR/Cas9. Intriguingly, in the absence of 27 PML, the IE1 protein could still localize to telomeres albeit less frequently. More 28 importantly, HHV-6A/B integration was impaired in the absence of PML, indicating that 29 it plays a role in the integration process. Taken together, we identified the first cellular 30 protein that aids in the integration of HHV-6A/B and shed light on this targeted integration 31 mechanism. 32 33 Author summary 34 Human herpesviruses type 6A and 6B are relatively common viruses whose infections can 35 be life threatening in patients with a compromised immune system. A rather unique feature 36 of these viruses is their ability to integrate their genome in human chromosomes.37 Integration takes place is a specialized region of the chromosomes known as telomeres, a 38 region that controls cellular lifespan. To date, the mechanisms leading to HHV-6A and 39 HHV-6B integration remain elusive. Our laboratory has identified that the IE1 protein of 3 40 HHV-6A and HHV-6B target the telomeres. Moreover, we have shown that IE1 associates 41 with a cellular protein, PML, that is responsible for the regulation of important cellular 42 mechanisms such as the life span of cells and DNA repair. Hence, we studied the role of 43 PML in HHV-6 integration. Our study demonstrates that in absence of PML, the HHV-6A 44 and HHV-6B integrate 50-70% less frequently. Thus, our study unveils the first cellular 45 protein involved in HHV-6A and HHV-6 chromosomal integration. 46 47 4 49 Human herpesviruses type 6A and 6B (HHV-6A/B) are members of the betaherpesvirinae 50 that were isolated in the 1980's. In 2013, the International Committee on Taxonomy of 51 Viruses recognized HHV-6A and HHV-6B as distinct viral species (1). HHV-6B is known 52 as the etiologic agent of exanthem subitum, a childhood disease whose symptoms include, 53 fever, occasional skin rash and respiratory distress (2). HHV-6A is much less characterized 54 than HHV-6B. Considering that many HHV-6A/B proteins share 90-95% homology, the

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“…Moreover, modification of PMLIV by SUMO positively regulates IFNβ synthesis through IRF3 activation, and it is required for protecting cells from virus infection [41]. PML-III and PML-IV also recruit Ubc9 to PML-NBs, and this recruitment has been shown to be essential for the increase in global SUMOylation induced by IFN [42]. This is not the unique mechanism that contributes to the increase in global SUMOylation upon IFN treatment.…”

Section: Sumo and Type I Ifn Responsesmentioning

confidence: 99%

SUMO and Cytoplasmic RNA Viruses: From Enemies to Best Friends

Motiam

Vidal

Seoane

et al. 2020

Advances in Experimental Medicine and Biology

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SUMO is a ubiquitin-like protein that covalently binds to lysine residues of target proteins and regulates many biological processes such as protein subcellular localization or stability, transcription, DNA repair, innate immunity, or antiviral defense. SUMO has a critical role in the signaling pathway governing type I interferon (IFN) production, and among the SUMOylation substrates are many IFN-induced proteins. The overall effect of IFN is increasing global SUMOylation, pointing to SUMO as part of the antiviral stress response. Viral agents have developed different mechanisms to counteract the antiviral activities exerted by SUMO, and some viruses have evolved to exploit the host SUMOylation machinery to modify their own proteins. The exploitation of SUMO has been mainly linked to nuclear replicating viruses due to the predominant nuclear localization of SUMO proteins and enzymes involved in SUMOylation. However, SUMOylation of numerous viral proteins encoded by RNA viruses replicating at the cytoplasm has been lately described. Whether nuclear localization of these viral proteins is required for their SUMOylation is unclear. Here, we summarize the studies on exploitation of SUMOylation by cytoplasmic RNA viruses and discuss about the requirement for nuclear localization of their proteins. Keywords SUMO · RNA viruses · Interferon SUMO ConjugationSUMOylation consists in the covalent attachment of the small ubiquitin-like modifier (SUMO) proteins to specific lysine residues of a target protein. This conjugation is an enzymatic process that occurs in cascade. The precursor SUMO proteins are proteolytically processed to the

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Promyelocytic Leukemia Protein (PML) Requirement for Interferon-induced Global Cellular SUMOylation

Cited by 27 publications

References 44 publications

The HSV-1 ubiquitin ligase ICP0: Modifying the cellular proteome to promote infection

The HSV-1 ubiquitin ligase ICP0: Modifying the cellular proteome to promote infection

Role of PML-Nuclear Bodies in Human Herpesvirus 6A and 6B Genome Integration

SUMO and Cytoplasmic RNA Viruses: From Enemies to Best Friends

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