Probing ubiquitin and SUMO conjugation and deconjugation

Ovaa, Huib; Vertegaal, Alfred C.O.

doi:10.1042/bst20170086

Cited by 22 publications

(20 citation statements)

References 99 publications

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“…In addition, SUMO proteases are known to be organelle-specific, with many localized to the nucleus. Therefore, it is difficult to compare deSUMOylation and deubiquitination (32,33).…”

Section: Discussionmentioning

confidence: 99%

Diverse fate of ubiquitin chain moieties: The proximal is degraded with the target, and the distal protects the proximal from removal and recycles

Sun

Mali

Singh

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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One of the enigmas in the ubiquitin (Ub) field is the requirement for a poly-Ub chain as a proteasomal targeting signal. The canonical chain appears to be longer than the distance between the two Ub-binding proteasomal receptors. Furthermore, genetic manipulation has shown that one receptor subunit is sufficient, which suggests that a single Ub can serve as a degradation signal. To shed light on this mystery, we chemically synthesized tetra-Ub, di-Ub (K48-based), and mono-Ub adducts of HA-α-globin, where the distal or proximal Ub moieties were tagged differentially with either Myc or Flag. When incubated in a crude cell extract, the distal Ub moiety in the tetra-Ub adduct was mostly removed by deubiquitinating enzymes (DUBs) and reconjugated to other substrates in the extract. In contrast, the proximal moiety was most likely degraded with the substrate. The efficacy of degradation was proportionate to the chain length; while tetra-Ub globin was an efficient substrate, with mono-Ub globin, we observed rapid removal of the Ub moiety with almost no degradation of the free globin. Taken together, these findings suggest that the proximal moieties are necessary for securing the association of the substrate with the proteasome along the proteolytic process, whereas the distal moieties are important in protecting the proximal moieties from premature deubiquitination. Interestingly, when the same experiment was carried out using purified 26S proteasome, mono- and tetra-Ub globin were similarly degraded, highlighting the roles of the entire repertoire of cellular DUBs in regulating the degradation of proteasomal substrates.

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“…In addition, SUMO proteases are known to be organelle-specific, with many localized to the nucleus. Therefore, it is difficult to compare deSUMOylation and deubiquitination (32,33).…”

Section: Discussionmentioning

confidence: 99%

Diverse fate of ubiquitin chain moieties: The proximal is degraded with the target, and the distal protects the proximal from removal and recycles

Sun

Mali

Singh

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Cell–cell and cell–matrix interactions require protein glycosylation . However, protein group modifications such as ubiquitination or SUMOylation provide a signal for protein degradation …”

Section: Role Of Ptms In Protein Functionmentioning

confidence: 99%

“…[12] For example, the phosphate group from adenosine triphosphate (ATP) is the material used for phosphorylation [13] and crotonyl-CoA is the donor for protein crotonylation. [10] Interestingly, PTMs appear to mediate crosstalk between cellular metabolic status and gene expression in response to various stimuli. For example, under starvation conditions, β-hydroxybutyrate generated at elevated levels by the liver attaches to histone proteins and epigenetically regulates a series of starvation responsive genes.…”

Section: The Origins Of Modification Groupsmentioning

confidence: 99%

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Advances of Proteomics in Novel PTM Discovery: Applications in Cancer Therapy

Wang

Zhang

et al. 2019

Small Methods

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Protein posttranslational modification (PTM) is a critical mechanism to enhance the diversity of protein species and functions in organisms. Currently, many different PTMs are discovered and found to be involved in a wide range of cellular processes. The aberrant regulation of PTM dynamics is reported to contribute to cancer development. Phosphorylation and acetylation are the best studied PTMs, and the application of high‐resolution mass spectrometry‐based proteomics and specific antibody‐based enrichment technologies significantly promotes novel PTM discovery. This review discusses methods for global PTM identification, including antibody‐based enrichment and chemical probe‐based identification. Several acylations, such as propionylation, butyrylation, succinylation, malonylation, and crotonylation, are recently found to influence both histone and nonhistone proteins and to be intimately linked with the progression of cancer. It is proposed that targeting novel PTM dynamics by pharmacological inhibitors has great potential for cancer therapy.

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“…In eukaryotic cells, SUMOylation is an important protein post-translational modification. The C-terminus of proteolytically activated small ubiquitin-like modifier (SUMO) is covalently bound to a lysine residue of the target protein by an isopeptide bond through a pathway that involves an E1-activating enzyme, an E2-conjugating enzyme, and a transfer to the target, in occasions with the support of a protein ligase [50]. The modification is reversed by a protease, which is also responsible for SUMO ripening.…”

Section: Parasite Biology and Reversible Post-translational Modificatmentioning

confidence: 99%

Role of Proteomics in the Study of Trypanosoma cruzi Biology

Francisco¹,

Gutiérrez²,

González³

2019

Biology of Trypanosoma Cruzi

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Proteomics is the science that studies the proteome, which corresponds to the global expression of proteins at a given time under determined conditions. In the last 20 years, proteomics has emerged as a powerful tool that has allowed the study of proteins that are expressed in the cell under normal or altered conditions as well as post-translational modifications, such as phosphorylation, glycosidation, acetylation, and methylation, among others. In this chapter, we present the main contributions of proteomics to the knowledge of Trypanosoma cruzi biology. Proteomes of all T. cruzi life cycle stages, secretomes/exoproteomes, post-translational modifications such as phosphorylation or acetylation and immunomes, interactomes, and glycomes are described. The role of proteomics in the identification of new chemotherapeutic targets and potential vaccine candidates will also be discussed.

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Probing ubiquitin and SUMO conjugation and deconjugation

Cited by 22 publications

References 99 publications

Diverse fate of ubiquitin chain moieties: The proximal is degraded with the target, and the distal protects the proximal from removal and recycles

Diverse fate of ubiquitin chain moieties: The proximal is degraded with the target, and the distal protects the proximal from removal and recycles

Advances of Proteomics in Novel PTM Discovery: Applications in Cancer Therapy

Role of Proteomics in the Study of Trypanosoma cruzi Biology

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