Human PARP1 substrates and regulators of its catalytic activity: An updated overview

Zhu, Tong; Zheng, Jinsen; Huang, Lingling; Wang, Yanhong; Yao, Di-Fei; Dai, Haibin

doi:10.3389/fphar.2023.1137151

Cited by 13 publications

(4 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human PARP1 is a multi-domain, 113-kDa protein that transfers ADP ribosyl groups from NAD + to acceptor chromatin and chromatin-associated proteins, and mediates base excision repair in DNA single-strand breaks. [35] Given its role in DNA repair processes, PARP1 is an attractive target as part of combination therapy for many cancers. [36] For the purpose of this proof-of-concept study, only its 39.6-kDa catalytic domain was used to test Olaparib response in ILIRA.…”

Section: Parp1cdmentioning

confidence: 99%

Investigating Protein Binding with the Isothermal Ligand‐induced Resolubilization Assay

Prout‐Holm,

van Walstijn,

Hitsman

et al. 2024

ChemBioChem

View full text Add to dashboard Cite

Target engagement assays typically detect and quantify the direct physical interaction of a protein of interest and its ligand through stability changes upon ligand binding. Commonly used target engagement methods detect ligand‐induced stability by subjecting samples to thermal or proteolytic stress. Here we describe a new variation to these approaches called Isothermal Ligand‐induced Resolubilization Assay (ILIRA), which utilizes lyotropic solubility stress to measure ligand binding through changes in target protein solubility. We identified distinct buffer systems and salt concentrations that compromised protein solubility for four diverse proteins: dihydrofolate reductase (DHFR), nucleoside diphosphate‐linked moiety X motif 5 (NUDT5), poly [ADP‐ribose] polymerase 1 (PARP1), and protein arginine N‐methyltransferase 1 (PRMT1). Ligand‐induced solubility rescue was demonstrated for these proteins, suggesting that ILIRA can be used as an additional target engagement technique. Differences in ligand‐induced protein solubility were assessed by Coomassie blue staining for SDS‐PAGE and dot blot, as well as by NanoOrange, Thioflavin T, and Proteostat fluorescence, thus offering flexibility for readout and assay throughput.

show abstract

Section: Parp1cdmentioning

confidence: 99%

Investigating Protein Binding with the Isothermal Ligand‐induced Resolubilization Assay

Prout‐Holm,

van Walstijn,

Hitsman

et al. 2024

ChemBioChem

View full text Add to dashboard Cite

show abstract

“…It is a nuclear enzyme that activates in response to DNA strand breaks and forms linear or branched PARs. These PARs are then linked with PARP, histones, DNA helicases, topoisomerases, single-strand break repair factors, base-excision repair factors and several transcription factors [ 108 ]. During the overproduction of PAR, and despite the activation of the DNA repair system, effective DNA repair does not occur, and cell death is potentiated due to repair-induced DNA decondensation.…”

Section: Nuclear Proteases In Parthanatosmentioning

confidence: 99%

New Perspectives on the Role of Nuclear Proteases in Cell Death Pathways

Frolova

Chepikova

Deviataikina

et al. 2023

Biology

View full text Add to dashboard Cite

Multiple factors can trigger cell death via various pathways, and nuclear proteases have emerged as essential regulators of these processes. While certain nuclear proteases have been extensively studied and their mechanisms of action are well understood, others remain poorly characterized. Regulation of nuclear protease activity is a promising therapeutic strategy that could selectively induce favorable cell death pathways in specific tissues or organs. Thus, by understanding the roles of newly discovered or predicted nuclear proteases in cell death processes, we can identify new pharmacological targets for improving therapeutic outcomes. In this article, we delved into the role of nuclear proteases in several types of cell death and explore potential avenues for future research and therapeutic development.

show abstract

“…ADP (ribosyl)ation is a post‐translational modification of biomolecules catalyzed by the ADP‐ribosyl transferase family of enzymes, commonly called PARPs. PARP enzymes transpose ADP‐ribose units from donor nicotinamide adenine dinucleotide (NAD+) molecules to a range of acceptor proteins, including proteins involved in DNA repair, transcription, histones, and chromatin modulators (Hassa & Hottiger, 2008; Zhu et al, 2023). The covalent attachment of ADP‐ribose subunits varies from monomers (MARylation) to polymers (PARylation) (Alemasova & Lavrik, 2019).…”

Section: Introductionmentioning

confidence: 99%

Exploring the interplay between PARP1 and circRNA biogenesis and function

Dhahri,

Fondufe‐Mittendorf

2023

WIREs RNA

View full text Add to dashboard Cite

PARP1 (poly‐ADP‐ribose polymerase 1) is a multidomain protein with a flexible and self‐folding structure that allows it to interact with a wide range of biomolecules, including nucleic acids and target proteins. PARP1 interacts with its target molecules either covalently via PARylation or non‐covalently through its PAR moieties induced by auto‐PARylation. These diverse interactions allow PARP1 to participate in complex regulatory circuits and cellular functions. Although the most studied PARP1‐mediated functions are associated with DNA repair and cellular stress response, subsequent discoveries have revealed additional biological functions. Based on these findings, PARP1 is now recognized as a major modulator of gene expression. Several discoveries show that this multifunctional protein has been intimately connected to several steps of mRNA biogenesis, from transcription initiation to mRNA splicing, polyadenylation, export, and translation of mRNA to proteins. Nevertheless, our understanding of PARP1's involvement in the biogenesis of both coding and noncoding RNA, notably circular RNA (circRNA), remains restricted. In this review, we outline the possible roles of PARP1 in circRNA biogenesis. A full examination of the regulatory roles of PARP1 in nuclear processes with an emphasis on circRNA may reveal new avenues to control dysregulation implicated in the pathogenesis of several diseases such as neurodegenerative disorders and cancers.This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Processing > Splicing Regulation/Alternative Splicing

show abstract

Human PARP1 substrates and regulators of its catalytic activity: An updated overview

Cited by 13 publications

References 114 publications

Investigating Protein Binding with the Isothermal Ligand‐induced Resolubilization Assay

Investigating Protein Binding with the Isothermal Ligand‐induced Resolubilization Assay

New Perspectives on the Role of Nuclear Proteases in Cell Death Pathways

Exploring the interplay between PARP1 and circRNA biogenesis and function

Contact Info

Product

Resources

About