Regulation of Poly(ADP-ribose) Polymerase-1-dependent Gene Expression through Promoter-directed Recruitment of a Nuclear NAD+ Synthase

Zhang, Tong; Berrocal, Jhoanna G.; Yao, Jie; DuMond, Michelle E.; Krishnakumar, Raga; Ruhl, Donald D.; Ryu, Keun Woo; Gamble, Matthew J.; Kraus, W. Lee

doi:10.1074/jbc.m111.304469

Cited by 100 publications

(90 citation statements)

References 51 publications

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“…It is found in the nucleus [124] where it is involved in many NADdependent nuclear processes. For example, PARP1 localized at target gene promoters recruits and interacts with NMNAT1 to regulate its activity by enhancing local NAD + availability [125,126]. Similar observations have been made for the other major nuclear NAD + -consuming enzyme, namely SIRT1 [127].…”

Section: Nad Biosynthetic Pathways and Enzymessupporting

confidence: 57%

NAD Biosynthesis in Humans - Enzymes, Metabolites and Therapeutic Aspects

Dölle¹,

Skoge²,

VanLinden³

et al. 2013

CTMC

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Section: Nad Biosynthetic Pathways and Enzymessupporting

confidence: 57%

NAD Biosynthesis in Humans - Enzymes, Metabolites and Therapeutic Aspects

Dölle¹,

Skoge²,

VanLinden³

et al. 2013

CTMC

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“…Although NAD + has historically been thought to pass freely from one cellular compartment to another, the results from recent studies (e.g., Zhang et al 2012;Cambronne et al 2016) and the fact that the three NMNATs have discreet and distinct subcellular localizations have challenged this view. Moreover, NAD + and PAR levels fluctuate during key biological processes, exemplified by a precipitous drop in both during the transition from mitotic cell growth to cellular differentiation during adipogenesis studies (Pekala et al 1981;Janssen and Hilz 1989;Luo et al 2017).…”

Section: Cellular Nad + Sensorsmentioning

confidence: 89%

PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

2017

Self Cite

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The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates. Supporting these advances is a host of methodological approaches from chemical biology, proteomics, genomics, cell biology, and genetics that have propelled new discoveries in the field. New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer. These studies have begun to reveal the promising ways in which PARPs may be targeted therapeutically for the treatment of disease. In this review, we discuss these topics and relate them to the future directions of the field.ADP-ribosylation is a reversible post-translational modification (PTM) of proteins resulting in the covalent attachment of a single ADP-ribose unit [i.e., mono(ADP-ribose) (MAR)] or polymers of ADP-ribose units [i.e., poly(ADP-ribose) (PAR)] on a variety of amino acid residues on target proteins (Gibson and Kraus 2012;Daniels et al. 2015a). This modification is mediated by a diverse group of ADPribosyl transferase (ADPRT) enzymes that use ADP-ribose units derived from β-NAD + to catalyze the ADP-ribosylation reaction. These enzymes include bacterial ADPRTs (e.g., cholera toxin and diphtheria toxin) as well as members of three different protein families in yeast and animals: (1) arginine-specific ecto-enzymes (ARTCs), (2) sirtuins, and (3) PAR polymerases (PARPs) . Surprisingly, a recent study showed that the bacterial toxin DarTG can ADP-ribosylate DNA . How this fits into the broader picture of cellular ADP-ribosylation has yet to be determined.In this review, we focus on the mono(ADP-ribosyl)ation (MARylation) and poly(ADP-ribosyl)ation (PARylation) of glutamate, aspartate, and lysine residues by PARP family members. While many reviews have been written on PARPs in the past decade, we highlight the current trends and ideas in the field, in particular those discoveries that have been published in the past 2-3 years.

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“…Moreover, the intranuclear localization of NAD + could provide an additional regulatory layer, by restricting NAD + distribution to "niches" of activity (88). This notion seems to be validated by the regulation of the NAD + -dependent nuclear enzyme poly (ADP ribose) polymerase-1 (PARP1), which recruits to its proximity the enzyme NMNAT1 involved in the NAD + salvage pathway, thereby allowing for local NAD + supply to support its activity on DNA (120). Interestingly, a role for PARP1 in enhancing the binding of CLOCK:BMAL1 to chromatin has been reported (121).…”

Section: Sirtuins: Metabolism and Epigenetics Convergementioning

confidence: 98%

Chromatin landscape and circadian dynamics: Spatial and temporal organization of clock transcription

Aguilar-Arnal

Sassone–Corsi

2014

Proc. Natl. Acad. Sci. U.S.A.

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Circadian rhythms drive the temporal organization of a wide variety of physiological and behavioral functions in ∼24-h cycles. This control is achieved through a complex program of gene expression. In mammals, the molecular clock machinery consists of interconnected transcriptional-translational feedback loops that ultimately ensure the proper oscillation of thousands of genes in a tissue-specific manner. To achieve circadian transcriptional control, chromatin remodelers serve the clock machinery by providing appropriate oscillations to the epigenome. Recent findings have revealed the presence of circadian interactomes, nuclear "hubs" of genome topology where coordinately expressed circadian genes physically interact in a spatial and temporal-specific manner. Thus, a circadian nuclear landscape seems to exist, whose interplay with metabolic pathways and clock regulators translates into specific transcriptional programs. Deciphering the molecular mechanisms that connect the circadian clock machinery with the nuclear landscape will reveal yet unexplored pathways that link cellular metabolism to epigenetic control.circadian rhythms | chromatin | epigenetics | nuclear organization

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Regulation of Poly(ADP-ribose) Polymerase-1-dependent Gene Expression through Promoter-directed Recruitment of a Nuclear NAD+ Synthase

Abstract: Background: NAD ϩ is required for nuclear enzymes that regulate chromatin and gene expression.

Cited by 100 publications

References 51 publications

NAD Biosynthesis in Humans - Enzymes, Metabolites and Therapeutic Aspects

NAD Biosynthesis in Humans - Enzymes, Metabolites and Therapeutic Aspects

PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

Chromatin landscape and circadian dynamics: Spatial and temporal organization of clock transcription

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