Hybrid Chains: A Collaboration of Ubiquitin and Ubiquitin-Like Modifiers Introducing Cross-Functionality to the Ubiquitin Code

Witting, Katharina F.; Ovaa, Huib; Mulder, Monique P. C.

doi:10.3389/fchem.2019.00931

Cited by 42 publications

(31 citation statements)

References 93 publications

(111 reference statements)

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“…Moreover, ubiquitin and certain Ubls, including SUMO, can form mixed chains, sometimes of complex and still ill-defined composition and topologies and can also be subjected to other post-translational modifications as discussed below. Elucidating the biochemical complexity and the biological consequences of what is now called the “ubiquitin code” is currently the object of intensive studies and still requires considerable efforts [ 33 , 34 , 35 , 36 ]. This implies that a number of conclusions from studies carried out before the advent of large-scale proteomics/modifomics might have to be reconsidered or, at least, nuanced.…”

Section: Sumoylation: a Principally Nuclear Post-translational Modmentioning

confidence: 99%

SUMO and Transcriptional Regulation: The Lessons of Large-Scale Proteomic, Modifomic and Genomic Studies

et al. 2021

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One major role of the eukaryotic peptidic post-translational modifier SUMO in the cell is transcriptional control. This occurs via modification of virtually all classes of transcriptional actors, which include transcription factors, transcriptional coregulators, diverse chromatin components, as well as Pol I-, Pol II- and Pol III transcriptional machineries and their regulators. For many years, the role of SUMOylation has essentially been studied on individual proteins, or small groups of proteins, principally dealing with Pol II-mediated transcription. This provided only a fragmentary view of how SUMOylation controls transcription. The recent advent of large-scale proteomic, modifomic and genomic studies has however considerably refined our perception of the part played by SUMO in gene expression control. We review here these developments and the new concepts they are at the origin of, together with the limitations of our knowledge. How they illuminate the SUMO-dependent transcriptional mechanisms that have been characterized thus far and how they impact our view of SUMO-dependent chromatin organization are also considered.

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Section: Sumoylation: a Principally Nuclear Post-translational Modmentioning

confidence: 99%

SUMO and Transcriptional Regulation: The Lessons of Large-Scale Proteomic, Modifomic and Genomic Studies

et al. 2021

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“…Several reports show that NEDD8 forms chains in vitro and in vivo, although the function of polyneddylation is not well defined yet [10,78,[84][85][86]. In addition, clear experimental evidence demonstrated that, upon proteotoxic stress, proteins are simultaneously modified by NEDD8 and ubiquitin mixed-chains.…”

Section: The Nedd8 "Enigma"mentioning

confidence: 99%

Old and New Concepts in Ubiquitin and NEDD8 Recognition

Santonico

2020

Biomolecules

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Post-translational modifications by ubiquitin and ubiquitin-like proteins (Ubls) have known roles in a myriad of cellular processes. Ubiquitin- and Ubl-binding domains transmit the information conferred by these post-translational modifications by recognizing functional surfaces and, when present, different chain structures. Numerous domains binding to ubiquitin have been characterized and their structures solved. Analogously, motifs selectively interacting with SUMO (small ubiquitin-like modifier) have been identified in several proteins and their role in SUMO-dependent processes investigated. On the other hand, proteins that specifically recognize other Ubl modifications are known only in a few cases. The high sequence identity between NEDD8 and ubiquitin has made the identification of specific NEDD8-binding domains further complicated due to the promiscuity in the recognition by several ubiquitin-binding domains. Two evolutionarily related domains, called CUBAN (cullin-binding domain associating with NEDD8) and CoCUN (cousin of CUBAN), have been recently described. The CUBAN binds monomeric NEDD8 and neddylated cullins, but it also interacts with di-ubiquitin chains. Conversely, the CoCUN domain only binds ubiquitin. CUBAN and CoCUN provide an intriguing example of how nature solved the issue of promiscuity versus selectivity in the recognition of these two highly related molecules. The structural information available to date suggests that the ancestor of CUBAN and CoCUN was a three-helix bundle domain that diversified in KHNYN (KH and NYN domain-containing) and N4BP1 (NEDD4-binding protein-1) by acquiring different features. Indeed, these domains diverged towards two recognition modes, that recall respectively the electrostatic interaction utilized by the E3-ligase RBX1/2 in the interaction with NEDD8, and the hydrophobic features described in the recognition of ubiquitin by CUE (coupling ubiquitin conjugation to ER degradation) domains. Intriguingly, CUBAN and CoCUN domains are only found in KHNYN and N4BP1, respectively, both proteins belonging to the PRORP family whose members are characterized by the combination of protein modules involved in RNA metabolism with domains mediating ubiquitin/NEDD8 recognition. This review recapitulates the current knowledge and recent findings of CUBAN and CoCUN domains and the proteins containing them.

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“…☆ In contrast to ubiquitin and other ULMs, ISG15 and FAT10 comprises two ubiquitin-like domains joined by a flexible linker [ 61 ]. There is accumulating evidence showing that ubiquitin and ULMs could generate hybrid chains, which seem to confer improved specificity and affinity towards their cognate receptors and to diversify the “ubiquitin code” [ 62 ].…”

Section: Figurementioning

confidence: 99%

Targeted Regulation of Nuclear Lamins by Ubiquitin and Ubiquitin-Like Modifiers

Blank

2020

Cells

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Nuclear lamins (NLs) are essential components of the animal cell nucleus involved in the regulation of a plethora of molecular and cellular processes. These include the nuclear envelope assembly and stability, mechanotransduction and chromatin organization, transcription, DNA replication, damage repair, and genomic integrity maintenance. Mutations in NLs can lead to the development of a wide range of distinct disease phenotypes, laminopathies, consisting of cardiac, neuromuscular, metabolic and premature aging syndromes. In addition, alterations in the expression of nuclear lamins were associated with different types of neoplastic diseases. Despite the importance and critical roles that NLs play in the diverse cellular activities, we only recently started to uncover the complexity of regulatory mechanisms governing their expression, localization and functions. This integrative review summarizes and discusses the recent findings on the emerging roles of ubiquitin and ubiquitin-like modifiers (ULMs) in the regulation of NLs, highlighting the intriguing molecular associations and cross-talks occurring between NLs and these regulatory molecules under physiological conditions and in the disease states.

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Hybrid Chains: A Collaboration of Ubiquitin and Ubiquitin-Like Modifiers Introducing Cross-Functionality to the Ubiquitin Code

Cited by 42 publications

References 93 publications

SUMO and Transcriptional Regulation: The Lessons of Large-Scale Proteomic, Modifomic and Genomic Studies

SUMO and Transcriptional Regulation: The Lessons of Large-Scale Proteomic, Modifomic and Genomic Studies

Old and New Concepts in Ubiquitin and NEDD8 Recognition

Targeted Regulation of Nuclear Lamins by Ubiquitin and Ubiquitin-Like Modifiers

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