Frameshift mutations of poly(adenosine diphosphate-ribose) polymerase genes in gastric and colorectal cancers with microsatellite instability

Kim, Min Sung; An, Chang Hyeok; Kim, Sung Soo; Yoo, Nam Jin; Lee, Sug Hyung

doi:10.1016/j.humpath.2010.11.020

Cited by 4 publications

(4 citation statements)

References 33 publications

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“…Curiously, one study associated lower TNKS1 mRNA levels in colon cancer with reduced survival [80]. Moreover, in subsets of gastric and colorectal cancers, deletion or duplication in exons of TNKS1 and TNKS2 were found [82]. Recent work points towards context-dependent effects of tankyrase inhibition on tumor development and progression.…”

Section: Tankyrase Involvement In Diseasesmentioning

confidence: 99%

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Tankyrases as drug targets

2013

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Tankyrase 1 and tankyrase 2 are poly(ADP-ribosyl)ases that are distinguishable from other members of the enzyme family by the structural features of the catalytic domain, and the presence of a sterile a-motif multimerization domain and an ankyrin repeat protein-interaction domain. Tankyrases are implicated in a multitude of cellular functions, including telomere homeostasis, mitotic spindle formation, vesicle transport linked to glucose metabolism, Wnt-b-catenin signaling, and viral replication. In these processes, tankyrases interact with target proteins, catalyze poly (ADP-ribosyl)ation, and regulate protein interactions and stability. The proposed roles of tankyrases in disease-relevant cellular processes have made them attractive drug targets. Recently, several inhibitors have been identified. The selectivity and potency of these small molecules can be rationalized by how they fit within the NAD + -binding groove of the catalytic domain. Some molecules bind to the nicotinamide subsite, such as generic diphtheria toxin-like ADP-ribosyltransferase inhibitors, whereas others bind to a distinct adenosine subsite that diverges from other diphtheria toxin-like ADP-ribosyltransferases and confers specificity. A highly potent dual-site inhibitor is also available. Within the last few years, tankyrase inhibitors have proved to be useful chemical probes and potential lead compounds, especially for specific cancers.

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Section: Tankyrase Involvement In Diseasesmentioning

confidence: 99%

“…Curiously, one study associated lower TNKS1 mRNA levels in colon cancer with reduced survival . Moreover, in subsets of gastric and colorectal cancers, deletion or duplication in exons of TNKS1 and TNKS2 were found .…”

Section: Roles Of Tankyrasesmentioning

confidence: 99%

Tankyrases as drug targets

2013

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“…Poly [adenosine diphosphate (ADP)-ribose] polymerases (PARPs) are one of the attractive and promising targets to treat several life-threatening diseases including cancer ( Kim et al, 2011 ; Bai and Virág, 2012 ; Langelier et al, 2018 ). The present study was undertaken to identify promising lead(s) against the mutated PARP12 enzyme.…”

Section: Discussionmentioning

confidence: 99%

“…Poly [adenosine diphosphate (ADP)-ribose] polymerases (PARPs) are the nuclear enzymes that regulate fundamental cellular processes involving protein degradation and gene expression ( Kim et al, 2011 ; Bai and Virag, 2012 ; Langelier et al, 2018 ). PARPs use nicotinamide adenine dinucleotide (NAD+) for the process of post-translation that modify substrate proteins with ADP-ribose, a vital process referred to as ADP ribosylation ( Carter-O'Connell and Cohen, 2015 ; Griffiths et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of PARP12 Inhibitors By Virtual Screening and Molecular Dynamics Simulations

et al. 2022

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Poly [adenosine diphosphate (ADP)-ribose] polymerases (PARPs) are members of a family of 17 enzymes that performs several fundamental cellular processes. Aberrant activity (mutation) in PARP12 has been linked to various diseases including inflammation, cardiovascular disease, and cancer. Herein, a large library of compounds (ZINC-FDA database) has been screened virtually to identify potential PARP12 inhibitor(s). The best compounds were selected on the basis of binding affinity scores and poses. Molecular dynamics (MD) simulation and binding free energy calculation (MMGBSA) were carried out to delineate the stability and dynamics of the resulting complexes. To this end, root means deviations, relative fluctuation, atomic gyration, compactness, covariance, residue-residue contact map, and free energy landscapes were studied. These studies have revealed that compounds ZINC03830332, ZINC03830554, and ZINC03831186 are promising agents against mutated PARP12.

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Crosstalk Between DNA Damage and Inflammation in the Multiple Steps of Gastric Carcinogenesis

Sokolova

Naumann

2019

Current Topics in Microbiology and Immunology

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Frameshift mutations of poly(adenosine diphosphate-ribose) polymerase genes in gastric and colorectal cancers with microsatellite instability

Cited by 4 publications

References 33 publications

Tankyrases as drug targets

Tankyrases as drug targets

Identification of PARP12 Inhibitors By Virtual Screening and Molecular Dynamics Simulations

Crosstalk Between DNA Damage and Inflammation in the Multiple Steps of Gastric Carcinogenesis

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