Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

More than Meets the ISG15: Emerging Roles in the DNA Damage Response and Beyond.

ABSTRACT: Maintenance of genome stability is a crucial priority for any organism. To meet this priority, robust signalling networks exist to facilitate error-free DNA replication and repair. These signalling cascades are subject to various regulatory post-translational modifications that range from simple additions of chemical moieties to the conjugation of ubiquitin-like proteins (UBLs). Interferon Stimulated Gene 15 (ISG15) is one such UBL. While classically thought of as a component of antiviral immunity, ISG15 has recently emerged as a regulator of genome stability, with key roles in the DNA damage response (DDR) to modulate p53 signalling and error-free DNA replication. Additional proteomic analyses and cancer-focused studies hint at wider-reaching, uncharacterised functions for ISG15 in genome stability. We review these recent discoveries and highlight future perspectives to increase our understanding of this multifaceted UBL in health and disease.

SUBMITTER: Sandy Z

PROVIDER: S-EPMC7698331 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

More than Meets the ISG15: Emerging Roles in the DNA Damage Response and Beyond.

Sandy Zac Z da Costa Isabelle Cristine IC Schmidt Christine K CK

Biomolecules 20201115 11

Maintenance of genome stability is a crucial priority for any organism. To meet this priority, robust signalling networks exist to facilitate error-free DNA replication and repair. These signalling cascades are subject to various regulatory post-translational modifications that range from simple additions of chemical moieties to the conjugation of ubiquitin-like proteins (UBLs). Interferon Stimulated Gene 15 (ISG15) is one such UBL. While classically thought of as a component of antiviral immuni ...[more]

PMID: 33203188

Similar Datasets

Brothers in arms: emerging roles of RNA epigenetics in DNA damage repair.

Project description:N6-methyladenosine (m6A) is a widespread posttranscriptional RNA modification that occurs in tRNA, rRNA, snRNA, viral RNAs, and more recently is shown to occur in mRNA in a dynamic, reversible manner. At the epicenter of RNA epigenetics, m6A influences essentially all stages of RNA metabolism. As a result, m6A modulates cell differentiation and pluripotency, cell cycle and tumorigenesis, and several types of stress responses, etc. A recent report by Shi and colleagues uncovers a novel pathway in which m6A RNA, its associated enzymes, and DNA polymerase ? constitute an early-response system that confers cellular resistance to ultraviolet irradiation, separate from the canonical nucleotide excision repair (NER) pathway that normally repairs UV-induced DNA damage.

| S-EPMC5418772 | biostudies-literature

Emerging roles of TET proteins and 5-hydroxymethylcytosines in active DNA demethylation and beyond.

Project description:Cytosine methylation is the major epigenetic modification of metazoan DNA. Although there is strong evidence that active DNA demethylation occurs in animal cells, the molecular details of this process are unknown. The recent discovery of the TET protein family (TET1-3) 5-methylcytosine hydroxylases has provided a new entry point to reveal the identity of the long-sought DNA demethylase. Here, we review the recent progress in understanding the function of TET proteins and 5-hydroxymethylcytosine (5hmC) through various biochemical and genomic approaches, the current evidence for a role of 5hmC as an early intermediate in active DNA demethylation and the potential functions of TET proteins and 5hmC beyond active DNA demethylation. We also discuss how future studies can extend our knowledge of this novel epigenetic modification.

| S-EPMC3219536 | biostudies-literature

Emerging Roles of Pleckstrin-2 Beyond Cell Spreading.

Project description:Pleckstrin-2 is a member of pleckstrin family with well-defined structural features that was first identified in 1999. Over the past 20 years, our understanding of PLEK2 biology has been limited to cell spreading. Recently, increasing evidences support that PLEK2 plays important roles in other cellular events beyond cell spreading, such as erythropoiesis, tumorigenesis and metastasis. It serves as a potential diagnostic and prognostic biomarker as well as an attractive target for the treatment of cancers. Herein, we summary the protein structure and molecular interactions of pleckstrin-2, with an emphasis on its regulatory roles in tumorigenesis.

| S-EPMC8637889 | biostudies-literature

Evolution, structure and emerging roles of C1ORF112 in DNA replication, DNA damage responses, and cancer.

Project description:The C1ORF112 gene initially drew attention when it was found to be strongly co-expressed with several genes previously associated with cancer and implicated in DNA repair and cell cycle regulation, such as RAD51 and the BRCA genes. The molecular functions of C1ORF112 remain poorly understood, yet several studies have uncovered clues as to its potential functions. Here, we review the current knowledge on C1ORF112 biology, its evolutionary history, possible functions, and its potential relevance to cancer. C1ORF112 is conserved throughout eukaryotes, from plants to humans, and is very highly conserved in primates. Protein models suggest that C1ORF112 is an alpha-helical protein. Interestingly, homozygous knockout mice are not viable, suggesting an essential role for C1ORF112 in mammalian development. Gene expression data show that, among human tissues, C1ORF112 is highly expressed in the testes and overexpressed in various cancers when compared to healthy tissues. C1ORF112 has also been shown to have altered levels of expression in some tumours with mutant TP53. Recent screens associate C1ORF112 with DNA replication and reveal possible links to DNA damage repair pathways, including the Fanconi anaemia pathway and homologous recombination. These insights provide important avenues for future research in our efforts to understand the functions and potential disease relevance of C1ORF112.

| S-EPMC8164572 | biostudies-literature

The molecular and physiological roles of ABCC6: more than meets the eye.

Project description:Abnormal mineralization occurs in the context of several common conditions, including advanced age, diabetes, hypercholesterolemia, chronic renal failure, and certain genetic conditions. Metabolic, mechanical, infectious, and inflammatory injuries promote ectopic mineralization through overlapping yet distinct molecular mechanisms of initiation and progression. The ABCC6 protein is an ATP-dependent transporter primarily found in the plasma membrane of hepatocytes. ABCC6 exports unknown substrates from the liver presumably for systemic circulation. ABCC6 deficiency is the primary cause for chronic and acute forms of ectopic mineralization described in diseases such as pseudoxanthoma elasticum (PXE), β-thalassemia, and generalized arterial calcification of infancy (GACI) in humans and dystrophic cardiac calcification (DCC) in mice. These pathologies are characterized by mineralization of cardiovascular, ocular, and dermal tissues. PXE and to an extent GACI are caused by inactivating ABCC6 mutations, whereas the mineralization associated with β-thalassemia patients derives from a liver-specific change in ABCC6 expression. DCC is an acquired phenotype resulting from cardiovascular insults (ischemic injury or hyperlipidemia) and secondary to ABCC6 insufficiency. Abcc6-deficient mice develop ectopic calcifications similar to both the human PXE and mouse DCC phenotypes. The precise molecular and cellular mechanism linking deficient hepatic ABCC6 function to distal ectopic mineral deposition is not understood and has captured the attention of many research groups. Our previously published work along with that of others show that ABCC6 influences other modulators of calcification and that it plays a much greater physiological role than originally thought.

| S-EPMC3520154 | biostudies-literature

MITF roles in the DNA damage response

Project description:This submission contains the mass spectrometry files for the manuscript by Romuald Binet et al. that describes the functional characterization of MITF roles in the DNA damage response. BioID experiments were performed from HEK293 cells and MS files were acquired on TripleTOF 5600 mass spectrometer. For questions, please contact Jean-Philippe Lambert (Jean-Philippe.Lambert@crchudequebec.ulaval.ca).

2022-03-23 | MSV000089109 | MassIVE

More than Meets the Eye: Understanding Perceptions of China Beyond the Favorable-Unfavorable Dichotomy.

Project description:How is China viewed by citizens of other countries? Popular polling data based on the feeling thermometer scale can reveal overall patterns of public sentiment toward China, but they do not necessarily capture the multidimensional preferences of the public. This article takes a deeper dive into a series of surveys conducted in Canada that covered a wide range of topics, from trade and investment to international leadership. Two broad conclusions follow. First, public perceptions of China are much more nuanced and conflicted than can be quickly gleaned from the simple dichotomy of "favorable versus unfavorable," especially as one moves from overall impressions to more specific policy issues. Second, misperceptions of China are widespread and may be difficult to overcome, especially among those who already view China negatively. At a time when countries around the world are grappling with the rise of China and its expanding global footprint, failure to account for these features in public opinion about China may lead to misguided policies.Supplementary informationThe online version contains supplementary material available at 10.1007/s12116-021-09320-1.

| S-EPMC7903215 | biostudies-literature

Emerging roles of the nucleolus in regulating the DNA damage response: the noncanonical DNA repair enzyme APE1/Ref-1 as a paradigmatical example.

Project description:SignificanceAn emerging concept in DNA repair mechanisms is the evidence that some key enzymes, besides their role in the maintenance of genome stability, display also unexpected noncanonical functions associated with RNA metabolism in specific subcellular districts (e.g., nucleoli). During the evolution of these key enzymes, the acquisition of unfolded domains significantly amplified the possibility to interact with different partners and substrates, possibly explaining their phylogenetic gain of functions.Recent advancesAfter nucleolar stress or DNA damage, many DNA repair proteins can freely relocalize from nucleoli to the nucleoplasm. This process may represent a surveillance mechanism to monitor the synthesis and correct assembly of ribosomal units affecting cell cycle progression or inducing p53-mediated apoptosis or senescence.Critical issuesA paradigm for this kind of regulation is represented by some enzymes of the DNA base excision repair (BER) pathway, such as apurinic/apyrimidinic endonuclease 1 (APE1). In this review, the role of the nucleolus and the noncanonical functions of the APE1 protein are discussed in light of their possible implications in human pathologies.Future directionsA productive cross-talk between DNA repair enzymes and proteins involved in RNA metabolism seems reasonable as the nucleolus is emerging as a dynamic functional hub that coordinates cell growth arrest and DNA repair mechanisms. These findings will drive further analyses on other BER proteins and might imply that nucleic acid processing enzymes are more versatile than originally thought having evolved DNA-targeted functions after a previous life in the early RNA world.

| S-EPMC3901381 | biostudies-literature

Emerging Roles of Metallothioneins in Beta Cell Pathophysiology: Beyond and Above Metal Homeostasis and Antioxidant Response.

Project description:Metallothioneins (MTs) are low molecular weight, cysteine-rich, metal-binding proteins whose precise biological roles have not been fully characterized. Existing evidence implicated MTs in heavy metal detoxification, metal ion homeostasis and antioxidant defense. MTs were thus categorized as protective effectors that contribute to cellular homeostasis and survival. This view has, however, been challenged by emerging evidence in different medical fields revealing novel pathophysiological roles of MTs, including inflammatory bowel disease, neurodegenerative disorders, carcinogenesis and diabetes. In the present focused review, we discuss the evidence for the role of MTs in pancreatic beta-cell biology and insulin secretion. We highlight the pattern of specific isoforms of MT gene expression in rodents and human beta-cells. We then discuss the mechanisms involved in the regulation of MTs in islets under physiological and pathological conditions, particularly type 2 diabetes, and analyze the evidence revealing adaptive and negative roles of MTs in beta-cells and the potential mechanisms involved. Finally, we underscore the unsettled questions in the field and propose some future research directions.

| S-EPMC7996892 | biostudies-literature

ISG15 in antiviral immunity and beyond.

Project description:The host response to viral infection includes the induction of type I interferons and the subsequent upregulation of hundreds of interferon-stimulated genes. Ubiquitin-like protein ISG15 is an interferon-induced protein that has been implicated as a central player in the host antiviral response. Over the past 15 years, efforts to understand how ISG15 protects the host during infection have revealed that its actions are diverse and pathogen-dependent. In this Review, we describe new insights into how ISG15 directly inhibits viral replication and discuss the recent finding that ISG15 modulates the host damage and repair response, immune response and other host signalling pathways. We also explore the viral immune-evasion strategies that counteract the actions of ISG15. These findings are integrated with a discussion of the recent identification of ISG15-deficient individuals and a cellular receptor for ISG15 that provides new insights into how ISG15 shapes the host response to viral infection.

| S-EPMC7097117 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data