Ubiquitin chain diversity at a glance

Akutsu, Masato; Đikić, Ivan; Bremm, Anja

doi:10.1242/jcs.183954

Cited by 463 publications

(390 citation statements)

References 85 publications

(103 reference statements)

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“…The K48-linked UB chains are the principal signal for UPS degradation, as will be mentioned below, but Parkin can also polyubiquitinate OMM substrates with K63-linked chains; this label is predominantly a tag for autophagy and recognized by different autophagy receptors by means of the UBD domain (Akutsu et al, 2016; Yamano et al, 2016). To date, five different autophagy receptors (p62, NBR1, Optineurin (OPTN), NDP52 and TAX1BP1) are able to recognize polyubiquitinated signals in PINK1/parkin-mediated mitophagy.…”

Section: Mitophagymentioning

confidence: 99%

Neuronal Mitophagy in Neurodegenerative Diseases

Martínez-Vicente

2017

Front. Mol. Neurosci.

164

115

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Neuronal homeostasis depends on the proper functioning of different quality control systems. All intracellular components are subjected to continuous turnover through the coordinated synthesis, degradation and recycling of their constituent elements. Autophagy is the catabolic mechanism by which intracellular cytosolic components, including proteins, organelles, aggregates and any other intracellular materials, are delivered to lysosomes for degradation. Among the different types of selective autophagy described to date, the process of mitophagy involves the selective autophagic degradation of mitochondria. In this way, mitophagy is responsible for basal mitochondrial turnover, but can also be induced under certain physiological or pathogenic conditions to eliminate unwanted or damaged mitochondria. Dysfunctional cellular proteolytic systems have been linked extensively to neurodegenerative diseases (ND) like Alzheimer’s disease (AD), Parkinson’s disease (PD), or Huntington’s disease (HD), with autophagic failure being one of the main factors contributing to neuronal cell death in these diseases. Neurons are particularly vulnerable to autophagic impairment as well as to mitochondrial dysfunction, due mostly to their particular high energy dependence and to their post-mitotic nature. The accurate and proper degradation of dysfunctional mitochondria by mitophagy is essential for maintaining control over mitochondrial quality and quantity in neurons. In this report, I will review the role of mitophagy in neuronal homeostasis and the consequences of its dysfunction in ND.

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Section: Mitophagymentioning

confidence: 99%

Neuronal Mitophagy in Neurodegenerative Diseases

Martínez-Vicente

2017

Front. Mol. Neurosci.

164

115

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“…E1 (ubiquitin activating enzymes), E2 (ubiquitin conjugating enzymes), and E3 (ubiquitin ligases) is necessary [3][4][5] (Figure 1). Ubiquitin is a small and highly conserved protein which can covalently attach to protein substrates as a single unit (monoubiquitin), multiple units (multi-monoubiquitins) or in the form of a polyubiquitin chain [6,7]. During polyubiquitylation, any of the seven lysine (K) residues (K6, K11, K27, K29, K33, K48, and K63) of ubiquitin can form linkages to others resulting into a sizeable chain comprising of sequentially linked ubiquitin molecules.…”

Section: Ubiquitin-proteasome Pathwaymentioning

confidence: 99%

“…Polyubiquitin chains formed by K-48 and K-63 linkage have been well understood and are widely reported in literature. K-48 linked chains directs the target protein for proteolysis via 26S proteasome, whereas K-63 linked polyubiquitin chains are involved in regulation of protein activity and signal transduction events [7]. Thus, ubiquitylation is a significant regulatory mechanism that is involved in various cellular processes such as apoptosis, oncogenesis, immune response, transcriptional DNA repair regulation, cell cycle control, embryonic developmentand intracellular signaling pathways [7].…”

Section: Ubiquitin-proteasome Pathwaymentioning

confidence: 99%

Future Application of Deubiquitylating Enzymes for Rapid and Efficient Cellular Reprogramming

Haq¹,

Ramakrishna²

2017

JSRT

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In stem cell pluripotency and differentiation, ubiquitylation and deubiquitylation modifications of stem cell core transcription proteinsis of high significance, as it influences stem cell fate determination. Two key enzymes i.e. an E3 ubiquitin ligase enzyme; known for tagging ubiquitin molecules to the target proteins for degradation, and the deubiquitylating enzyme (DUB), that counteracts the proteolysis, have to be well balanced for cellular homeostasis. Interestingly, the notion of DUBs enhancing the stability and half-life of stem cell core transcription factors has presented a new vision about significance of applying DUBs to control stem cell fate determination and cellular reprogramming. In this review, we propose the applications of DUBs along with stem cells core transcription factors i.e. Oct4, Sox2, Klf4, c-Myc, Nanog and Lin28 for an efficient generation of protein induced pluripotent stem cells.

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“…However, ubiquitination is also involved in diverse cellular functions such as transcriptional regulation, the immune response, apoptosis, cell cycle control, oncogenesis, embryonic development, preimplantation, and intracellular signaling pathways. 31 …”

Section: Ubiquitin-proteasome Pathwaymentioning

confidence: 99%

Regulation of pluripotency and differentiation by deubiquitinating enzymes

et al. 2016

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Post-translational modifications (PTMs) of stemness-related proteins are essential for stem cell maintenance and differentiation. In stem cell self-renewal and differentiation, PTM of stemness-related proteins is tightly regulated because the modified proteins execute various stem cell fate choices. Ubiquitination and deubiquitination, which regulate protein turnover of several stemness-related proteins, must be carefully coordinated to ensure optimal embryonic stem cell maintenance and differentiation. Deubiquitinating enzymes (DUBs), which specifically disassemble ubiquitin chains, are a central component in the ubiquitin-proteasome pathway. These enzymes often control the balance between ubiquitination and deubiquitination. To maintain stemness and achieve efficient differentiation, the ubiquitination and deubiquitination molecular switches must operate in a balanced manner. Here we summarize the current information on DUBs, with a focus on their regulation of stem cell fate determination and deubiquitinase inhibition as a therapeutic strategy. Furthermore, we discuss the possibility of using DUBs with defined stem cell transcription factors to enhance cellular reprogramming efficiency and cell fate conversion. Our review provides new insight into DUB activity by emphasizing their cellular role in regulating stem cell fate. This role paves the way for future research focused on specific DUBs or deubiquitinated substrates as key regulators of pluripotency and stem cell differentiation.

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Ubiquitin chain diversity at a glance

Cited by 463 publications

References 85 publications

Neuronal Mitophagy in Neurodegenerative Diseases

Neuronal Mitophagy in Neurodegenerative Diseases

Future Application of Deubiquitylating Enzymes for Rapid and Efficient Cellular Reprogramming

Regulation of pluripotency and differentiation by deubiquitinating enzymes

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