Identification of a Non-covalent Ternary Complex Formed by PIAS1, SUMO1, and UBC9 Proteins Involved in Transcriptional Regulation

Mascle, Xavier H.; Lussier-Price, Mathieu; Cappadocia, Laurent; Estephan, Patricia; Raiola, Luca; Omichinski, James G.; Aubry, Muriel

doi:10.1074/jbc.m113.486845

Cited by 26 publications

(38 citation statements)

References 92 publications

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“…Furthermore, Pias1 phosphorylation enhanced this ternary complex formation by engaging a phospho-SIM in the SUMO1 B interaction (87). Interestingly, earlier studies have shown that this phosphorylation influences the transcriptional coregulatory activities of Pias1 and other Pias family members (88), even though Pias1's SIM phosphorylation was proposed not to influence its catalytic activity.…”

Section: Insights Into E3-dependent Catalysismentioning

confidence: 99%

“…Some class I SIMs demonstrate paralog specificity, probably through additional interactions adjacent to the hydrophobic core (75,76,(83)(84)(85)(86)(87). Also, the class II DPP9, but not Ubc9, shows specificity for SUMO1, while the class III HERC2 displays preference for SUMO1 (80,81).…”

Section: Non-covalent Sumo Interactionsmentioning

confidence: 99%

“…Further evidence for the significance of a scaffold SUMO B interaction comes from Pias1, which interacts via its SIM, C-terminally flanking the SP-RING with a SUMO1 B on the backside of Ubc9 (87). Furthermore, Pias1 phosphorylation enhanced this ternary complex formation by engaging a phospho-SIM in the SUMO1 B interaction (87).…”

Section: Insights Into E3-dependent Catalysismentioning

confidence: 99%

“…One exciting example is the acetylation of SUMO1 at Lys37 or SUMO3 at Lys33 (SUMO2 Lys32) that controls selected SUMO-SIM interactions by neutralizing the positive charges of amino acid residues surrounding the SIM docking site (49). Moreover, introduction of a negative charge by phosphorylation of serine residues adjacent to the SIM hydrophobic core enhances the non-covalent interactions with SUMO via Lys39, His43 and Lys46 in SUMO1 and His17, Lys35 and His37 in SUMO3 (76,(86)(87)(88)(89). A more detailed functional and structural analysis will be required to fully understand the complexity of non-covalent SUMO interactions and their regulation by PTMs.…”

Section: Non-covalent Sumo Interactionsmentioning

confidence: 99%

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SUMO conjugation – a mechanistic view

Pichler

Fatouros

Lee

et al. 2017

Biomolecular Concepts

218

223

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Abstract:The regulation of protein fate by modification with the small ubiquitin-related modifier (SUMO) plays an essential and crucial role in most cellular pathways. Sumoylation is highly dynamic due to the opposing activities of SUMO conjugation and SUMO deconjugation. SUMO conjugation is performed by the hierarchical action of E1, E2 and E3 enzymes, while its deconjugation involves SUMO-specific proteases. In this review, we summarize and compare the mechanistic principles of how SUMO gets conjugated to its substrate. We focus on the interplay of the E1, E2 and E3 enzymes and discuss how specificity could be achieved given the limited number of conjugating enzymes and the thousands of substrates.

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Section: Insights Into E3-dependent Catalysismentioning

confidence: 99%

Section: Non-covalent Sumo Interactionsmentioning

confidence: 99%

Section: Insights Into E3-dependent Catalysismentioning

confidence: 99%

Section: Non-covalent Sumo Interactionsmentioning

confidence: 99%

See 2 more Smart Citations

SUMO conjugation – a mechanistic view

Pichler

Fatouros

Lee

et al. 2017

Biomolecular Concepts

218

223

View full text Add to dashboard Cite

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“…The SOCS family of genes is known to bring about ubiquitination-mediated degradation of target proteins such as STAT, thus downregulating IFN-␥ response (51,52). The PIAS family of proteins sumoylate several known immune modulators, thus relegating them to a new cellular location and resulting in a loss of function (53)(54)(55).…”

Section: Discussionmentioning

confidence: 99%

The WNT Signaling Pathway Contributes to Dectin-1-Dependent Inhibition of Toll-Like Receptor-Induced Inflammatory Signature

Trinath

Holla

Mahadik

et al. 2014

Molecular and Cellular Biology

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Macrophages regulate cell fate decisions during microbial challenges by carefully titrating signaling events activated by innate receptors such as dectin-1 or Toll-like receptors (TLRs). Here, we demonstrate that dectin-1 activation robustly dampens TLRinduced proinflammatory signature in macrophages. Dectin-1 induced the stabilization of ␤-catenin via spleen tyrosine kinase (Syk)-reactive oxygen species (ROS) signals, contributing to the expression of WNT5A. Subsequently, WNT5A-responsive protein inhibitors of activated STAT (PIAS-1) and suppressor of cytokine signaling 1 (SOCS-1) mediate the downregulation of IRAK-1, IRAK-4, and MyD88, resulting in decreased expression of interleukin 12 (IL-12), IL-1␤, and tumor necrosis factor alpha (TNF-␣). In vivo activation of dectin-1 with pathogenic fungi or ligand resulted in an increased bacterial burden of Mycobacteria, Klebsiella, Staphylococcus, or Escherichia, with a concomitant decrease in TLR-triggered proinflammatory cytokines. All together, our study establishes a new role for dectin-1-responsive inhibitory mechanisms employed by virulent fungi to limit the proinflammatory environment of the host.

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A PIAS1 Protective Variant S510G Delays polyQ Disease Onset by Modifying Protein Homeostasis

et al. 2021

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Background Polyglutamine (polyQ) diseases are dominant neurodegenerative diseases caused by an expansion of the polyQ‐encoding CAG repeats in the disease‐causing gene. The length of the CAG repeats is the major determiner of the age at onset (AO) of polyQ diseases, including Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3). Objective We set out to identify common genetic variant(s) that may affect the AO of polyQ diseases. Methods Three hundred thirty‐seven patients with HD or SCA3 were enrolled for targeted sequencing of 583 genes implicated in proteinopathies. In total, 16 genes were identified as containing variants that are associated with late AO of polyQ diseases. For validation, we further investigate the variants of PIAS1 because PIAS1 is an E3 SUMO (small ubiquitin‐like modifier) ligase for huntingtin (HTT), the protein linked to HD. Results Biochemical analyses revealed that the ability of PIAS1S510G to interact with mutant huntingtin (mHTT) was less than that of PIAS1WT, resulting in lower SUMOylation of mHTT and lower accumulation of insoluble mHTT. Genetic knock‐in of PIAS1S510G in a HD mouse model (R6/2) ameliorated several HD‐like deficits (including shortened life spans, poor grip strength and motor coordination) and reduced neuronal accumulation of mHTT. Conclusions Our findings suggest that PIAS1 is a genetic modifier of polyQ diseases. The naturally occurring variant, PIAS1S510G, is associated with late AO in polyQ disease patients and milder disease severity in HD mice. Our study highlights the possibility of targeting PIAS1 or pathways governing protein homeostasis as a disease‐modifying approach for treating patients with HD. © 2021 International Parkinson and Movement Disorder Society

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Identification of a Non-covalent Ternary Complex Formed by PIAS1, SUMO1, and UBC9 Proteins Involved in Transcriptional Regulation

Cited by 26 publications

References 92 publications

SUMO conjugation – a mechanistic view

SUMO conjugation – a mechanistic view

The WNT Signaling Pathway Contributes to Dectin-1-Dependent Inhibition of Toll-Like Receptor-Induced Inflammatory Signature

A PIAS1 Protective Variant S510G Delays polyQ Disease Onset by Modifying Protein Homeostasis

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