Recent Highlights: Onco Viral Exploitation of the SUMO System

Mattoscio, Domenico; Medda, Alessandro; Chiocca, Susanna

doi:10.21775/cimb.035.001

Cited by 9 publications

(6 citation statements)

References 108 publications

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“…SUMOylation is also involved in viral infection by modifying viral proteins or cellular proteins, which are important in antiviral defense [ 152 , 153 ]. Some viral proteins such as adenovirus type 5 (Ad5) E1B-55K [ 154 ], Kaposi’s sarcoma-associated herpesvirus (KSHV) K-bZIP [ 155 ], and the Ad5 E4-ORF3 [ 156 ], were identified as SUMO E3 ligases by an in vitro SUMOylation assay.…”

Section: The Classification Of Sumo E3 Ligasesmentioning

confidence: 99%

The Role of SUMO E3 Ligases in Signaling Pathway of Cancer Cells

Shi

et al. 2022

IJMS

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Small ubiquitin-like modifier (SUMO)ylation is a reversible post-translational modification that plays a crucial role in numerous aspects of cell physiology, including cell cycle regulation, DNA damage repair, and protein trafficking and turnover, which are of importance for cell homeostasis. Mechanistically, SUMOylation is a sequential multi-enzymatic process where SUMO E3 ligases recruit substrates and accelerate the transfer of SUMO onto targets, modulating their interactions, localization, activity, or stability. Accumulating evidence highlights the critical role of dysregulated SUMO E3 ligases in processes associated with the occurrence and development of cancers. In the present review, we summarize the SUMO E3 ligases, in particular, the novel ones recently identified, and discuss their regulatory roles in cancer pathogenesis.

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Section: The Classification Of Sumo E3 Ligasesmentioning

confidence: 99%

The Role of SUMO E3 Ligases in Signaling Pathway of Cancer Cells

Shi

et al. 2022

IJMS

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“…Besides, activity of the immune system-associated factor signal transducer and activator of transcription 5 (STAT5) is also under the control of sumoylation (reviewed in [ 72 ]), as well as the cGAS-STING pathway involved in sensing of cytosolic DNA [ 42 , 73 ], and the inflammasome [ 74 , 75 ]. In relation to immunity, a number of oncogenic viruses have demonstrated to hijack the sumoylation pathway for their own benefit, participating in infection, persistence and transformation of host cells [ 76 ]. Among them are hepatitis B and C viruses, human papillomavirus, Epstein–Barr virus, Kaposi’s sarcoma-associated herpesviruses, human T-cell leukemia virus type 1 and Merkel cell polyomavirus.…”

Section: Sumo In Cancermentioning

confidence: 99%

Cancer-Associated Dysregulation of Sumo Regulators: Proteases and Ligases

Lara-Ureña

Jafari

García‐Domínguez

2022

IJMS

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SUMOylation is a post-translational modification that has emerged in recent decades as a mechanism involved in controlling diverse physiological processes and that is essential in vertebrates. The SUMO pathway is regulated by several enzymes, proteases and ligases being the main actors involved in the control of sumoylation of specific targets. Dysregulation of the expression, localization and function of these enzymes produces physiological changes that can lead to the appearance of different types of cancer, depending on the enzymes and target proteins involved. Among the most studied proteases and ligases, those of the SENP and PIAS families stand out, respectively. While the proteases involved in this pathway have specific SUMO activity, the ligases may have additional functions unrelated to sumoylation, which makes it more difficult to study their SUMO-associated role in cancer process. In this review we update the knowledge and advances in relation to the impact of dysregulation of SUMO proteases and ligases in cancer initiation and progression.

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“…The modification of proteins by the addition of the Small Ubiquitin-like Modifiers (SUMOs) is an important mechanism of regulating both viral and cellular proteins that can affect their activity, localization, or stability, and can promote protein-protein interactions. SUMOylation of cellular proteins is often associated with antiviral and stress responses and viruses are known to encode proteins that induce SUMOylation or target SUMOylated cellular proteins for degradation [23,[36][37][38][39][40][41].…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus BGLF2 commandeers RISC to interfere with cellular miRNA function

et al. 2022

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The Epstein-Barr virus (EBV) BGLF2 protein is a tegument protein with multiple effects on the cellular environment, including induction of SUMOylation of cellular proteins. Using affinity-purification coupled to mass-spectrometry, we identified the miRNA-Induced Silencing Complex (RISC), essential for miRNA function, as a top interactor of BGLF2. We confirmed BGLF2 interaction with the Ago2 and TNRC6 components of RISC in multiple cell lines and their co-localization in cytoplasmic bodies that also contain the stress granule marker G3BP1. In addition, BGLF2 expression led to the loss of processing bodies in multiple cell types, suggesting disruption of RISC function in mRNA regulation. Consistent with this observation, BGLF2 disrupted Ago2 association with multiple miRNAs. Using let-7 miRNAs as a model, we tested the hypothesis that BGLF2 interfered with the function of RISC in miRNA-mediated mRNA silencing. Using multiple reporter constructs with 3’UTRs containing let-7a regulated sites, we showed that BGLF2 inhibited let-7a miRNA activity dependent on these 3’UTRs, including those from SUMO transcripts which are known to be regulated by let-7 miRNAs. In keeping with these results, we showed that BGLF2 increased the cellular level of unconjugated SUMO proteins without affecting the level of SUMO transcripts. Such an increase in free SUMO is known to drive SUMOylation and would account for the effect of BGLF2 in inducing SUMOylation. We further showed that BGLF2 expression inhibited the loading of let-7 miRNAs into Ago2 proteins, and conversely, that lytic infection with EBV lacking BGLF2 resulted in increased interaction of let-7a and SUMO transcripts with Ago2, relative to WT EBV infection. Therefore, we have identified a novel role for BGLF2 as a miRNA regulator and shown that one outcome of this activity is the dysregulation of SUMO transcripts that leads to increased levels of free SUMO proteins and SUMOylation.

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Recent Highlights: Onco Viral Exploitation of the SUMO System

Cited by 9 publications

References 108 publications

The Role of SUMO E3 Ligases in Signaling Pathway of Cancer Cells

The Role of SUMO E3 Ligases in Signaling Pathway of Cancer Cells

Cancer-Associated Dysregulation of Sumo Regulators: Proteases and Ligases

Epstein-Barr Virus BGLF2 commandeers RISC to interfere with cellular miRNA function

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