NEDD8 ultimate buster‐1 regulates the abundance of TRF1 at telomeres by promoting its proteasomal degradation

Jeong, Yu Young; Her, Joonyoung; Chung, In Kwon

doi:10.1002/1873-3468.12221

Cited by 4 publications

(2 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 114 ] Moreover, NUB1 specifically interacts with telomeric protein TRF1 to facilitate its proteasomal degradation. [ 115 ] Interestingly, the NUB1 binding proteins just described are all found in phase‐separated compartments: synphilin‐1 and α‐synuclein undergo LLPS before maturing into insoluble Lewy bodies‐like aggregates [ 116,117 ] ; tau LLPS may be an intermediate step toward aggregate formation [ 118 ] ; telomeres and TRF1 cluster in a class of PML bodies specialized in telomere length maintenance. [ 119 ] NUB1 comprises multiple UBA domains and 13 cysteines, providing the mulitivalency and oligomerization (from potential disulfide bonds) needed for LLPS.…”

Section: Do Other Ub‐binding or Ub‐like Binding Shuttle Proteins Funcmentioning

confidence: 99%

Ubiquitin‐Modulated Phase Separation of Shuttle Proteins: Does Condensate Formation Promote Protein Degradation?

Dao

Castañeda

2020

BioEssays

View full text Add to dashboard Cite

Liquid-liquid phase separation (LLPS) has recently emerged as a possible mechanism that enables ubiquitin-binding shuttle proteins to facilitate the degradation of ubiquitinated substrates via distinct protein quality control (PQC) pathways. Shuttle protein LLPS is modulated by multivalent interactions among their various domains as well as heterotypic interactions with polyubiquitin chains. Here, the properties of three different shuttle proteins (hHR23B, p62, and UBQLN2) are closely examined, unifying principles for the molecular determinants of their LLPS are identified, and how LLPS is connected to their functions is discussed. Evidence supporting LLPS of other shuttle proteins is also found. In this review, it is proposed that shuttle protein LLPS leads to spatiotemporal regulation of PQC activities by mediating the recruitment of PQC machinery (including proteasomes or autophagic components) to biomolecular condensates, assembly/disassembly of condensates, selective enrichment of client proteins, and extraction of ubiquitinated proteins from condensates in cells.

show abstract

Section: Do Other Ub‐binding or Ub‐like Binding Shuttle Proteins Funcmentioning

confidence: 99%

Ubiquitin‐Modulated Phase Separation of Shuttle Proteins: Does Condensate Formation Promote Protein Degradation?

Dao

Castañeda

2020

BioEssays

View full text Add to dashboard Cite

show abstract

“…Several proteins have been identified as targets for NUB1-dependant degradation, and in some cases, degradation can occur independently of substrate NEDDylation. The telomeric protein TRF1 was found to be degraded by the proteasome in a NUB1 dependent process, and while degradation of TRF1 could occur following NEDDylation [72], it was also possible to be degraded following MLN4924 treatment suggesting both NEDD8 dependent and independent pathways of degradation. The degradation of Huntington protein (Htt) requires NUB1, but is thought to occur through an indirect mechanism whereby NUB1 interacts with Htt and recruits a NEDDylated CRL directly to Htt, facilitating polyubiquitination and proteasome-mediated degradation of Htt [73].…”

Section: Protein Degradationmentioning

confidence: 99%

The Many Potential Fates of Non-Canonical Protein Substrates Subject to NEDDylation

Vijayasimha

Dolan

2021

Cells

View full text Add to dashboard Cite

Neuronal precursor cell-expressed developmentally down-regulated protein 8 (NEDD8) is a ubiquitin-like protein (UBL) whose canonical function involves binding to, and thus, activating Cullin–Ring finger Ligases (CRLs), one of the largest family of ubiquitin ligases in the eukaryotic cell. However, in recent years, several non-canonical protein substrates of NEDD8 have been identified. Here we attempt to review the recent literature regarding non-canonical NEDDylation of substrates with a particular focus on how the covalent modification of NEDD8 alters the protein substrate. Like much in the study of ubiquitin and UBLs, there are no clear and all-encompassing explanations to satisfy the textbooks. In some instances, NEDD8 modification appears to alter the substrates localization, particularly during times of stress. NEDDylation may also have conflicting impacts upon a protein’s stability: some reports indicate NEDDylation may protect against degradation whereas others show NEDDylation can promote degradation. We also examine how many of the in vitro studies measuring non-canonical NEDDylation were conducted and compare those conditions to those which may occur in vivo, such as cancer progression. It is likely that the conditions used to study non-canonical NEDDylation are similar to some types of cancers, such as glioblastoma, colon and rectal cancers, and lung adenocarcinomas. Although the full outcomes of non-canonical NEDDylation remain unknown, our review of the literature suggests that researchers keep an open mind to the situations where this modification occurs and determine the functional impacts of NEDD8-modification to the specific substrates which they study.

show abstract

Protein neddylation and its role in health and diseases

Zhang,

Yu,

et al. 2024

Sig Transduct Target Ther

View full text Add to dashboard Cite

NEDD8 (Neural precursor cell expressed developmentally downregulated protein 8) is an ubiquitin-like protein that is covalently attached to a lysine residue of a protein substrate through a process known as neddylation, catalyzed by the enzyme cascade, namely NEDD8 activating enzyme (E1), NEDD8 conjugating enzyme (E2), and NEDD8 ligase (E3). The substrates of neddylation are categorized into cullins and non-cullin proteins. Neddylation of cullins activates CRLs (cullin RING ligases), the largest family of E3 ligases, whereas neddylation of non-cullin substrates alters their stability and activity, as well as subcellular localization. Significantly, the neddylation pathway and/or many neddylation substrates are abnormally activated or over-expressed in various human diseases, such as metabolic disorders, liver dysfunction, neurodegenerative disorders, and cancers, among others. Thus, targeting neddylation becomes an attractive strategy for the treatment of these diseases. In this review, we first provide a general introduction on the neddylation cascade, its biochemical process and regulation, and the crystal structures of neddylation enzymes in complex with cullin substrates; then discuss how neddylation governs various key biological processes via the modification of cullins and non-cullin substrates. We further review the literature data on dysregulated neddylation in several human diseases, particularly cancer, followed by an outline of current efforts in the discovery of small molecule inhibitors of neddylation as a promising therapeutic approach. Finally, few perspectives were proposed for extensive future investigations.

show abstract

NEDD8 ultimate buster‐1 regulates the abundance of TRF1 at telomeres by promoting its proteasomal degradation

Cited by 4 publications

References 43 publications

Ubiquitin‐Modulated Phase Separation of Shuttle Proteins: Does Condensate Formation Promote Protein Degradation?

Ubiquitin‐Modulated Phase Separation of Shuttle Proteins: Does Condensate Formation Promote Protein Degradation?

The Many Potential Fates of Non-Canonical Protein Substrates Subject to NEDDylation

Protein neddylation and its role in health and diseases

Contact Info

Product

Resources

About