Mechanisms governing PARP expression, localization, and activity in cells

Sanderson, Daniel J.; Cohen, Michael S.

doi:10.1080/10409238.2020.1818686

Cited by 25 publications

(18 citation statements)

References 87 publications

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“…Besides, the Trp-Trp-Glu motif (WWE) domain is another important regulatory domain sharing in some PARPs, including PARP7, PARP11, PARP12, PARP13, and PARP14. In contrast, others fall outside of these groups as their domains are either unique (PARP4 and PARP16) or uncharacterized (PARP6 and PARP8) (2). According to their catalytic activities, PARPs are categorized as poly-ADP-ribose polymerases, mono-ADP-ribose polymerases, and inactive ADPribose polymerases.…”

Section: Introductionmentioning

confidence: 99%

The Critical Role of PARPs in Regulating Innate Immune Responses

et al. 2021

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Poly (adenosine diphosphate-ribose) polymerases (PARPs) are a family of proteins responsible for transferring ADP-ribose groups to target proteins to initiate the ADP-ribosylation, a highly conserved and fundamental post-translational modification in all organisms. PARPs play important roles in various cellular functions, including regulating chromatin structure, transcription, replication, recombination, and DNA repair. Several studies have recently converged on the widespread involvement of PARPs and ADP-Ribosylation reaction in mammalian innate immunity. Here, we provide an overview of the emerging roles of PARPs family and ADP-ribosylation in regulating the host’s innate immune responses involved in cancers, pathogenic infections, and inflammations, which will help discover and design new molecular targets for cancers, pathogenic infections, and inflammations.

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Section: Introductionmentioning

confidence: 99%

The Critical Role of PARPs in Regulating Innate Immune Responses

et al. 2021

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“…The enzymes that catalyze ADPRylation belong to a 17-member family known as the poly-(ADP-ribose) polymerases (PARPs), named after PARP1, the first and best characterized member of the PARP family [ 1 , 2 ]. PARPs can be divided into two major subfamilies: 5 PARPs that catalyze the formation of polymers of ADP-ribose (poly-ADP-ribosylation or PARylation) and 11 PARPs that transfer a single unit of ADP-ribose (mono-ADP-ribosylation or MARylation) [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of PARP6 Function in Knockout Mice and Patients with Developmental Delay

Vermehren-Schmaedick

Huang

Levinson

et al. 2021

Cells

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PARP6, a member of a family of enzymes (17 in humans) known as poly-ADP-ribose polymerases (PARPs), is a neuronally enriched PARP. While previous studies from our group show that Parp6 is a regulator of dendrite morphogenesis in rat hippocampal neurons, its function in the nervous system in vivo is poorly understood. Here, we describe the generation of a Parp6 loss-of-function mouse model for examining the function of Parp6 during neurodevelopment in vivo. Using CRISPR-Cas9 mutagenesis, we generated a mouse line that expressed a Parp6 truncated variant (Parp6TR) in place of Parp6WT. Unlike Parp6WT, Parp6TR is devoid of catalytic activity. Homozygous Parp6TR do not exhibit obvious neuromorphological defects during development, but nevertheless die perinatally. This suggests that Parp6 catalytic activity is important for postnatal survival. We also report PARP6 mutations in six patients with several neurodevelopmental disorders, including microencephaly, intellectual disabilities, and epilepsy. The most severe mutation in PARP6 (C563R) results in the loss of catalytic activity. Expression of Parp6C563R in hippocampal neurons decreases dendrite morphogenesis. To gain further insight into PARP6 function in neurons we also performed a BioID proximity labeling experiment in hippocampal neurons and identified several microtubule-binding proteins (e.g., MAP-2) using proteomics. Taken together, our results suggest that PARP6 is an essential microtubule-regulatory gene in mice, and that the loss of PARP6 catalytic activity has detrimental effects on neuronal function in humans.

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“…Second, the ADPribosylation ability of every ART is naturally linked to the availability of NAD + and its Km for NAD + that varies from enzyme to enzyme and ranges from only few µM to several hundred µM [93][94][95][96]. Finally, comparable to other enzymes, mono-ARTs can be regulated by additional signaling events and binding to cofactors ( [35,97,98] and reviewed in [99,100]). The regulation of MARylation by ART expression and NAD + affinity or NAD + competition is discussed in the following sections.…”

Section: Regulation Of Cellular Marylationmentioning

confidence: 99%

Uncovering the Invisible: Mono-ADP-ribosylation Moved into the Spotlight

Hopp

Hottiger

2021

Cells

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Adenosine diphosphate (ADP)-ribosylation is a nicotinamide adenine dinucleotide (NAD+)-dependent post-translational modification that is found on proteins as well as on nucleic acids. While ARTD1/PARP1-mediated poly-ADP-ribosylation has extensively been studied in the past 60 years, comparably little is known about the physiological function of mono-ADP-ribosylation and the enzymes involved in its turnover. Promising technological advances have enabled the development of innovative tools to detect NAD+ and NAD+/NADH (H for hydrogen) ratios as well as ADP-ribosylation. These tools have significantly enhanced our current understanding of how intracellular NAD dynamics contribute to the regulation of ADP-ribosylation as well as to how mono-ADP-ribosylation integrates into various cellular processes. Here, we discuss the recent technological advances, as well as associated new biological findings and concepts.

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Mechanisms governing PARP expression, localization, and activity in cells

Cited by 25 publications

References 87 publications

The Critical Role of PARPs in Regulating Innate Immune Responses

The Critical Role of PARPs in Regulating Innate Immune Responses

Characterization of PARP6 Function in Knockout Mice and Patients with Developmental Delay

Uncovering the Invisible: Mono-ADP-ribosylation Moved into the Spotlight

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