Met1-linked ubiquitin signalling in health and disease: inflammation, immunity, cancer, and beyond

Jahan, Akhee Sabiha; Elbæk, Camilla Reiter; Damgaard, Rune Busk

doi:10.1038/s41418-020-00676-w

Cited by 42 publications

(48 citation statements)

References 158 publications

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“…Linear ubiquitin chains (also known as Met1‐linked ubiquitin or M1‐Ub) have in the past decade emerged as critically important for controlling vital immune receptor pathways leading to efficient activation of the IκB kinase (IKK) complex and the nuclear factor κB (NF‐κB) transcription factor [1]. The formation of M1‐Ub chains is catalysed by the linear ubiquitin chain assembly complex (LUBAC) [2], which is comprised of three proteins: haem‐oxidized IRP2 ubiquitin ligase‐1 (HOIL‐1), HOIL‐1‐interacting protein (HOIP), and shank‐associated RH domain interactor (SHARPIN).…”

Section: Figmentioning

confidence: 99%

“…Efficient activation of the IKK complex and transcription of inflammatory genes by NF‐κB rely on nondegradative Lys63‐linked ubiquitin (K63‐Ub) and M1‐Ub signals [1]. In activated immune receptor complexes, K63‐Ub and M1‐Ub are formed as hybrid (or mixed) chains — in which LUBAC generates M1‐Ub on pre‐existing K63‐Ub chains (Fig.…”

Section: Figmentioning

confidence: 99%

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Ester‐linked ubiquitination by HOIL‐1 controls immune signalling by shaping the linear ubiquitin landscape

Pruneda

Damgaard

2021

The FEBS Journal

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Ester‐linked ubiquitination of serine or threonine residues – or even lipids – has emerged as a new regulatory earmark in cell signalling. Petrova et al. (2021) now reveal that ubiquitin esterification by the atypical ubiquitin ligase HOIL‐1, a component of the LUBAC complex, is critical for proper formation of linear ubiquitin chains and control of immune signalling in T cells and macrophages. Surprisingly, ester‐linked ubiquitination can either promote or inhibit linear ubiquitin conjugation and cytokine production depending on the receptor and immune cell engaged. Comment on: https://doi.org/10.1111/febs.15896.

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Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Ester‐linked ubiquitination by HOIL‐1 controls immune signalling by shaping the linear ubiquitin landscape

Pruneda

Damgaard

2021

The FEBS Journal

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“…Modification of proteins by ubiquitin is involved in the regulation of various relevant biological processes, including apoptosis, cell cycle progression, differentiation, transcription, signal transduction, DNA repair and autophagy [12][13][14][15][16][17][18][19]. Coherently, dysregulation of the UPS is associated with severe pathologies, such as neurodegenerative and immune disorders and cancer [20][21][22][23][24][25][26]. Indeed, the autophagic process, reviewed in [27][28][29][30], strongly relies on the protein degradation pathway.…”

Section: The Ubiquitin Systemmentioning

confidence: 99%

Emerging roles of the HECT-type E3 ubiquitin ligases in hematological malignancies

et al. 2021

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Ubiquitination-mediated proteolysis or regulation of proteins, ultimately executed by E3 ubiquitin ligases, control a wide array of cellular processes, including transcription, cell cycle, autophagy and apoptotic cell death. HECT-type E3 ubiquitin ligases can be distinguished from other subfamilies of E3 ubiquitin ligases because they have a C-terminal HECT domain that directly catalyzes the covalent attachment of ubiquitin to their substrate proteins. Deregulation of HECT-type E3-mediated ubiquitination plays a prominent role in cancer development and chemoresistance. Several members of this subfamily are indeed frequently deregulated in human cancers as a result of genetic mutations and altered expression or activity. HECT-type E3s contribute to tumorigenesis by regulating the ubiquitination rate of substrates that function as either tumour suppressors or oncogenes. While the pathological roles of the HECT family members in solid tumors are quite well established, their contribution to the pathogenesis of hematological malignancies has only recently emerged. This review aims to provide a comprehensive overview of the involvement of the HECT-type E3s in leukemogenesis.

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“…Various studies have proposed that ubiquitylation has a significant regulatory function and performs an important role in inflammation, cell division, signal transduction, hypersensitive response, proteasomal degradation, downregulation, transcription, and deoxyribonucleic acid repairing [ 11 , 12 , 13 , 14 , 15 , 16 ]. Ubiquitylation has also been implicated in a wide range of diseases such as periodontal disease, cancer, Alzheimer, Parkinson, immune disorders [ 17 , 18 , 19 , 20 ]. According to the literature, ubiquitination performs an essential role in plant biology, including hormone signaling, light perception, embryogenesis, reflection of an unfavorable environment, prevention of pathogens, epigenetic regulation, subcellular localization of plant immunity-associated proteins, and their interactions with other cellular molecules [ 21 , 22 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

UbiComb: A Hybrid Deep Learning Model for Predicting Plant-Specific Protein Ubiquitylation Sites

Siraj

Lim

Tayara

et al. 2021

Genes

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Protein ubiquitylation is an essential post-translational modification process that performs a critical role in a wide range of biological functions, even a degenerative role in certain diseases, and is consequently used as a promising target for the treatment of various diseases. Owing to the significant role of protein ubiquitylation, these sites can be identified by enzymatic approaches, mass spectrometry analysis, and combinations of multidimensional liquid chromatography and tandem mass spectrometry. However, these large-scale experimental screening techniques are time consuming, expensive, and laborious. To overcome the drawbacks of experimental methods, machine learning and deep learning-based predictors were considered for prediction in a timely and cost-effective manner. In the literature, several computational predictors have been published across species; however, predictors are species-specific because of the unclear patterns in different species. In this study, we proposed a novel approach for predicting plant ubiquitylation sites using a hybrid deep learning model by utilizing convolutional neural network and long short-term memory. The proposed method uses the actual protein sequence and physicochemical properties as inputs to the model and provides more robust predictions. The proposed predictor achieved the best result with accuracy values of 80% and 81% and F-scores of 79% and 82% on the 10-fold cross-validation and an independent dataset, respectively. Moreover, we also compared the testing of the independent dataset with popular ubiquitylation predictors; the results demonstrate that our model significantly outperforms the other methods in prediction classification results.

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Met1-linked ubiquitin signalling in health and disease: inflammation, immunity, cancer, and beyond

Cited by 42 publications

References 158 publications

Ester‐linked ubiquitination by HOIL‐1 controls immune signalling by shaping the linear ubiquitin landscape

Ester‐linked ubiquitination by HOIL‐1 controls immune signalling by shaping the linear ubiquitin landscape

Emerging roles of the HECT-type E3 ubiquitin ligases in hematological malignancies

UbiComb: A Hybrid Deep Learning Model for Predicting Plant-Specific Protein Ubiquitylation Sites

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