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The β-NAD + salvage pathway and PKC-mediated signaling influence localized PARP-1 activity and CTCF Poly(ADP)ribosylation

Overview of attention for article published in Oncotarget, August 2017
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Title
The β-NAD + salvage pathway and PKC-mediated signaling influence localized PARP-1 activity and CTCF Poly(ADP)ribosylation
Published in
Oncotarget, August 2017
DOI 10.18632/oncotarget.19841
Pubmed ID
Authors

David J P Henderson, Jj L Miranda, Beverly M Emerson

Abstract

Poly(ADP)ribosylation (PARylation) of the chromatin architectural protein CTCF is critical for CTCF-dependent regulation of chromatin boundary and insulator elements. Loss of CTCF PARylation results in epigenetic silencing of certain tumor suppressor genes through destabilization of nearby chromatin boundaries. We investigated the metabolic and mechanistic processes that regulate PARP-1-mediated CTCF PARylation in human cancer cell lines and discovered a key role for the expression and activity of β-NAD+ salvage enzymes, NAMPT and NMNAT-1. These enzymes are downregulated in cells that exhibit reduced CTCF PARylation, resulting in a decreased concentration of nuclear β-NAD+. In these cells, decreased NMNAT-1 expression is enforced by a proteasome-mediated feedback loop resulting in degradation of NMNAT-1, transcriptional repression of NAMPT, and suppression of PARP-1 activity. Interestingly, dePARylated CTCF is associated in a stable protein complex with PARP-1 and NMNAT-1 in cancer cells harboring silenced tumor suppressor genes. Although the metabolic context in these cells favors suppression of PARP-1 activity, CTCF PARylation can be restored by Protein Kinase C (PKC) signaling. PKC induces dissociation of the catalytically inactive PARP-1/NMNAT-1/CTCF protein complex and phosphorylation of NMNAT-1, which stimulates its proteasome-mediated degradation. Our findings suggest that CTCF PARylation is underpinned by a cellular metabolic context engendered by regulation of the β-NAD+ salvage pathway in which NMNAT-1 acts as a rheostat to control localized β-NAD+ synthesis at CTCF/PARP-1 complexes.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 32%
Student > Master 3 14%
Student > Doctoral Student 2 9%
Student > Postgraduate 2 9%
Researcher 1 5%
Other 1 5%
Unknown 6 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 36%
Agricultural and Biological Sciences 4 18%
Medicine and Dentistry 2 9%
Pharmacology, Toxicology and Pharmaceutical Science 1 5%
Immunology and Microbiology 1 5%
Other 1 5%
Unknown 5 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 October 2018.
All research outputs
#17,917,778
of 23,006,268 outputs
Outputs from Oncotarget
#7,714
of 14,344 outputs
Outputs of similar age
#227,703
of 317,579 outputs
Outputs of similar age from Oncotarget
#527
of 1,061 outputs
Altmetric has tracked 23,006,268 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 14,344 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one is in the 40th percentile – i.e., 40% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 317,579 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1,061 others from the same source and published within six weeks on either side of this one. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.