RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair

Moreno-Onate, Marta; Herrero-Ruiz, Andrés; García-Domínguez, Mario; Cortés‐Ledesma, Felipe; Ruiz, José F.

doi:10.1016/j.jmb.2020.03.020

Cited by 7 publications

(5 citation statements)

References 55 publications

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“…SIR2A is a PfSUMO conjugate as validated by in vitro experiments (Tonkin et al, 2009). the production of new merozoites, that rapidly egress from RBCs to invade new erythrocytes, which amplify exponentially the symptoms of malaria disease (Striepen et al, 2007;Absalon et al, 2018;de Jong et al, 2020;Molina-Franky et al, 2020), Figure 1B.…”

Section: Roles Of the Sumoylation Machinery Within The Life Cycle Of P Falciparummentioning

confidence: 96%

“…Classically, SUMO conjugation consists of the covalent linkage of SUMO protein on lysine residues of a protein substrate, which is triggered by the sequential action of three enzymes: heterodimeric E1-activating enzyme (Aos1/Uba2), E2-conjugating enzyme (Ubc9), and SUMO-E3 ligase, in an ATP-dependent manner ( Streich and Lima, 2014 ; Pichler et al, 2017 ; Varejão et al, 2020 ). SUMO-conjugated maintains the fine-tuning of cellular functions by altering intracellular compartmentalization or modulating the protein stability, enzymatic activity, and interactions affinity ( Moreno-Oñate et al, 2020 ; Sohn et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Targeting SUMOylation in Plasmodium as a Potential Target for Malaria Therapy

Oliveira

Kronenberger

Palmisano

et al. 2021

Front. Cell. Infect. Microbiol.

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Malaria is a parasitic disease that represents a public health problem worldwide. Protozoans of the Plasmodium genus are responsible for causing malaria in humans. Plasmodium species have a complex life cycle that requires post-translational modifications (PTMs) to control cellular activities temporally and spatially and regulate the levels of critical proteins and cellular mechanisms for maintaining an efficient infection and immune evasion. SUMOylation is a PTM formed by the covalent linkage of a small ubiquitin-like modifier protein to the lysine residues on the protein substrate. This PTM is reversible and is triggered by the sequential action of three enzymes: E1-activating, E2-conjugating, and E3 ligase. On the other end, ubiquitin-like-protein-specific proteases in yeast and sentrin-specific proteases in mammals are responsible for processing SUMO peptides and for deconjugating SUMOylated moieties. Further studies are necessary to comprehend the molecular mechanisms and cellular functions of SUMO in Plasmodium. The emergence of drug-resistant malaria parasites prompts the discovery of new targets and antimalarial drugs with novel mechanisms of action. In this scenario, the conserved biological processes regulated by SUMOylation in the malaria parasites such as gene expression regulation, oxidative stress response, ubiquitylation, and proteasome pathways, suggest PfSUMO as a new potential drug target. This mini-review focuses on the current understanding of the mechanism of action of the PfSUMO during the coordinated multi-step life cycle of Plasmodium and discusses them as attractive new target proteins for the development of parasite-specific inhibitors and therapeutic intervention toward malaria disease.

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Section: Roles Of the Sumoylation Machinery Within The Life Cycle Of P Falciparummentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Targeting SUMOylation in Plasmodium as a Potential Target for Malaria Therapy

Oliveira

Kronenberger

Palmisano

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…RanBP2 enriches at kinetochores and the mitotic spindle having essential functions in nucleoplasmic transport during interphase [ 124 ] and chromosome segregation mitosis [ 125 ]. In addition, new functions are emerging in DNA damage, as recent research has reported the E3 activity of RanBP2 in DNA polymerase lambda SUMOylation [ 110 ]. All these functions match with knockout mice studies showing that RanBP2 −/− mice were unviable, highlighting the essential role of RanBP2 [ 126 ].…”

Section: Sumoylationmentioning

confidence: 99%

Insights in Post-Translational Modifications: Ubiquitin and SUMO

Salas-Lloret

González-Prieto

2022

IJMS

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Both ubiquitination and SUMOylation are dynamic post-translational modifications that regulate thousands of target proteins to control virtually every cellular process. Unfortunately, the detailed mechanisms of how all these cellular processes are regulated by both modifications remain unclear. Target proteins can be modified by one or several moieties, giving rise to polymers of different morphology. The conjugation cascades of both modifications comprise a few activating and conjugating enzymes but close to thousands of ligating enzymes (E3s) in the case of ubiquitination. As a result, these E3s give substrate specificity and can form polymers on a target protein. Polymers can be quickly modified forming branches or cleaving chains leading the target protein to its cellular fate. The recent development of mass spectrometry(MS) -based approaches has increased the understanding of ubiquitination and SUMOylation by finding essential modified targets in particular signaling pathways. Here, we perform a concise overview comprising from the basic mechanisms of both ubiquitination and SUMOylation to recent MS-based approaches aimed to find specific targets for particular E3 enzymes.

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“…The SUMO E3 ligase RanBP2 is a large nucleoporin possessing SUMO-stabilizing activity, which is involved in several types of cancer ( 65 , 66 ). RanBP2 is part of a larger complex, consisting of SUMO-modified Ran GTPase activating protein 1 (RanGAP1), the GTP-hydrolysis activating factor for the GTPase RAN ( 67 ).…”

Section: Aberrant Function Of the Sumoylation Pathway And Its Targets In Hematological Malignanciesmentioning

confidence: 99%

“…RanBP2 is part of a larger complex, consisting of SUMO-modified Ran GTPase activating protein 1 (RanGAP1), the GTP-hydrolysis activating factor for the GTPase RAN ( 67 ). It has been shown that RanBP2 mediates the SUMOylation of Polλ at K27, which promotes the incorporation of Polλ into the nucleus DNA damage repair group with appropriate polymerase activity ( 65 ). RanBP2 also promotes the SUMOylation of endogenous tripartite motif-containing protein 5 (TRIM5α) on K84 within the predicted phosphorylated SUMOylation motif in the cytoplasm, thereby forming a complex of RanGAP1/Ubc9/TRIM5α at the nuclear pore ( 68 ).…”

Section: Aberrant Function Of the Sumoylation Pathway And Its Targets In Hematological Malignanciesmentioning

confidence: 99%

Novel insights into the impact of the SUMOylation pathway in hematological malignancies (Review)

Qian

Yang

2021

Int J Oncol

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The small ubiquitin-like modifier (SUMO) system serves an important role in the regulation of protein stability and function. SUMOylation sustains the homeostatic equilibrium of protein function in normal tissues and numerous types of tumor. Accumulating evidence has revealed that SUMO enzymes participate in carcinogenesis via a series of complex cellular or extracellular processes. The present review outlines the physiological characteristics of the SUMOylation pathway and provides examples of SUMOylation participation in different cancer types, including in hematological malignancies (leukemia, lymphoma and myeloma). It has been indicated that the SUMO pathway may influence chromosomal instability, cell cycle progression, apoptosis and chemical drug resistance. The present review also discussed the possible relationship between SUMOylation and carcinogenic mechanisms, and evaluated their potential as biomarkers and therapeutic targets in the diagnosis and treatment of hematological malignancies. Developing and investigating inhibitors of SUMO conjugation in the future may offer promising potential as novel therapeutic strategies.

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RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair

Cited by 7 publications

References 55 publications

Targeting SUMOylation in Plasmodium as a Potential Target for Malaria Therapy

Targeting SUMOylation in Plasmodium as a Potential Target for Malaria Therapy

Insights in Post-Translational Modifications: Ubiquitin and SUMO

Novel insights into the impact of the SUMOylation pathway in hematological malignancies (Review)

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