Evidence map›Paper›PMID 27041572›Full record

ArticleOncogene2016

Interaction of hepatitis B virus X protein with PARP1 results in inhibition of DNA repair in hepatocellular carcinoma.

T-Y Na, N-L Ka, H Rhee, D Kyeong, M-H Kim, J K Seong, Y N Park, M-O Lee

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In one paragraph

Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 46 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

T-Y NaCollege of Pharmacy and Bio-MAX Institute, Seoul National University, Seoul, Korea.
N-L KaCollege of Pharmacy and Bio-MAX Institute, Seoul National University, Seoul, Korea.
H RheeDepartment of Pathology, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, Korea.
D KyeongCollege of Veterinary Medicine, Interdisciplinary Program for Bioinformatics and Program for Cancer Biology, Seoul National University and Korea Mouse Phenotyping Center, Seoul, Korea.
M-H KimCollege of Pharmacy and Bio-MAX Institute, Seoul National University, Seoul, Korea.
J K SeongCollege of Veterinary Medicine, Interdisciplinary Program for Bioinformatics and Program for Cancer Biology, Seoul National University and Korea Mouse Phenotyping Center, Seoul, Korea.
Y N ParkDepartment of Pathology, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, Korea.
M-O LeeCollege of Pharmacy and Bio-MAX Institute, Seoul National University, Seoul, Korea.
Seoul National University · KRYonsei University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatitis B virus X protein (HBx) contributes to the development of hepatocellular carcinoma (HCC), probably by regulating activities of many host or viral proteins through protein-protein interactions. In this study, we identified poly(ADP-ribose) polymerase (PARP1), a crucial factor in DNA repair, as an HBx-interacting protein using a proteomics approach. Coimmunoprecipitation and proximity ligation assays confirmed the binding and colocalization of HBx and PARP1 in the nucleus. The carboxyl-terminus of HBx protein bound to the catalytic domain of PARP1, and this binding reduced the enzymatic activity of PARP1 in both in vitro and in vivo assays. HBx interrupted the binding of PARP1 to Sirt6, which catalyzes the mono-ADP-ribosylation required for DNA repair. Consistently, overexpression of HBx inhibited the clearance of γH2AX DNA repair foci generated under oxidative stress in Chang liver cells. Recruitment of the DNA repair complex to the site-specific double-strand breaks was inhibited in the presence of HBx, when measured by laser microirradiation assay and damage-specific chromatin immunoprecipitation assays. Consequently, HBx increased signs of DNA damage such as accumulation of 8-hydroxy-2'-deoxyguanosine and comet formation, which were reversed by overexpression of PARP1 and/or Sirt6. Finally, the interaction between PARP1 and Sirt6 was markedly lower in the livers of HBx-transgenic mice and specimens obtained from HCC patients to compare with the corresponding control. Our data suggest that the physical interaction of HBx and PARP1 accelerates DNA damage by inhibiting recruitment of the DNA repair complex to the damaged DNA sites, which may lead to the onset of hepatocarcinogenesis.

Indexed as

AnimalsCarcinogenesisCarcinoma, HepatocellularDNA-Binding ProteinsDNA DamageDNA RepairGene Expression Regulation, NeoplasticHepatitis B virusHep G2 CellsHistonesHumansLiver NeoplasmsMiceMice, TransgenicPoly (ADP-Ribose) Polymerase-1SirtuinsDNA-Binding ProteinsH2AX protein, humanhepatitis B virus X proteinHistonesPARP1 protein, humanPoly (ADP-Ribose) Polymerase-1SIRT6 protein, humanSirtuinsTrans-ActivatorsViral Regulatory and Accessory Proteins

Identifiers

PMID27041572
OpenAlexW2339723611

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.