Evidence map›Paper›PMID 33468657›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington's disease.

Eva L Morozko, Charlene Smith-Geater, Alejandro Mas Monteys, Subrata Pradhan, Ryan G Lim, Peter Langfelder, Marketta Kachemov, Jayesh A Kulkarni, Josh Zaifman, Austin Hill and 20 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
4.2field-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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
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  17. Poly ADP-ribose signaling is dysregulated in Huntington disease.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 6 institutions in 2 countries.

Eva L MorozkoDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.
Charlene Smith-GeaterDepartment of Psychiatry and Human Behavior, University of California, Irvine, CA 92697.ORCID https://orcid.org/0000-0003-2136-4420
Alejandro Mas MonteysRaymond G. Perelman Center for Cell and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Subrata PradhanDepartment of Neurology, University of Texas Medical Branch, Galveston, TX 77555.ORCID https://orcid.org/0000-0002-3636-2615
Ryan G LimInstitute of Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697.ORCID https://orcid.org/0000-0001-6388-5158
Peter LangfelderDepartment of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, CA 90095.ORCID https://orcid.org/0000-0003-3418-4146
Marketta KachemovDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.ORCID https://orcid.org/0000-0001-7954-8930
Jayesh A KulkarniDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Josh ZaifmanDepartment of Chemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z1.
Austin HillIncisive Genetics Inc., Vancouver, BC, Canada V6A 0H9.
Jennifer T StocksdaleDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.ORCID https://orcid.org/0000-0002-4304-6266
Pieter R CullisDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.ORCID https://orcid.org/0000-0001-9586-2508
Jie WuDepartment of Biological Chemistry, University of California, Irvine, CA 92697.
Joseph OchabaDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.
Ricardo MiramontesInstitute of Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697.
Anirban ChakrabortyDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555.
Tapas K HazraDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555.
Alice LauDepartment of Psychiatry and Human Behavior, University of California, Irvine, CA 92697.
Sophie St-CyrRaymond G. Perelman Center for Cell and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104.ORCID https://orcid.org/0000-0003-2448-9202
Iliana OrellanaSue and Bill Gross Stem Cell Institute, University of California, Irvine, CA 92697.
Lexi KopanDepartment of Psychiatry and Human Behavior, University of California, Irvine, CA 92697.
Keona Q WangDepartment of Psychiatry and Human Behavior, University of California, Irvine, CA 92697.ORCID https://orcid.org/0000-0002-7715-2489
Sylvia YeungInstitute of Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697.
Blair R LeavittCentre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4.
Jack C ReidlingInstitute of Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697.
X William YangCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095.
Joan S SteffanDepartment of Psychiatry and Human Behavior, University of California, Irvine, CA 92697.ORCID https://orcid.org/0000-0003-2467-6294
Beverly L DavidsonRaymond G. Perelman Center for Cell and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Partha S SarkarDepartment of Neurology, University of Texas Medical Branch, Galveston, TX 77555.
Leslie M ThompsonDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697; lmthomps@uci.edu.
University of California, Irvine · USThe University of Texas Medical Branch at Galveston · USUniversity of British Columbia · CAChildren's Hospital of Philadelphia · USUniversity of California, Los Angeles · USIncisive Genetics (Canada) · CA

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Neuron and Glial Cellular Signatures from Normal and Diseased iPS Cells-SupplementU54NS091046 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI FINKBEINER, STEVEN M, FRAENKEL, ERNEST · 2014 to 2020
$11.7M
Novel mouse genetic models to study modifiers of Huntington’s diseaseR01NS113612 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2019 to 2023
$3.2M
Genomic and functional analysis of transcriptome changes in Huntington's DiseaseR01NS076631 · NINDS · UNIVERSITY OF IOWA · PI DAVIDSON, BEVERLY L., ROSS, CHRISTOPHER A · 2013 to 2017
$3.2M
Neuroregulatory Mechanisms of PIAS1 and Implications for Huntington's DiseaseR01NS090390 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAVIDSON, BEVERLY L., THOMPSON, LESLIE MICHELS · 2015 to 2018
$1.8M
Pathogenic Role of DNA-Damage Response Pathway in the Diabetic RetinaR01EY026089 · NEI · UNIVERSITY OF TEXAS MED BR GALVESTON · PI SARKAR, PARTHA S · 2016 to 2019
$1.4M
Pathogenic impact of Huntington phosphorylation in Huntington's DiseaseR01NS072453 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI STEFFAN, JOAN SAWYER · 2012 to 2015
$1.3M
Neuroregulatory Mechanisms of PIAS1 and Implications for Huntington's DiseaseR56NS090390 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI THOMPSON, LESLIE MICHELS · 2014 to 2014
$565k
Pathogenic impact of Huntingtin phosphorylation in Huntington's DiseaseR56NS072453 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI STEFFAN, JOAN SAWYER · 2017 to 2017
$377k
NCI NIH HHS P30 CA062203NEI NIH HHS R01 EY026089NINDS NIH HHS R01 NS072453NINDS NIH HHS R01 NS076631NINDS NIH HHS R01 NS090390NINDS NIH HHS R01 NS113612NINDS NIH HHS R56 NS072453NINDS NIH HHS R56 NS090390NINDS NIH HHS U54 NS091046
6 · The paper itself

Abstract

DNA damage repair genes are modifiers of disease onset in Huntington's disease (HD), but how this process intersects with associated disease pathways remains unclear. Here we evaluated the mechanistic contributions of protein inhibitor of activated STAT-1 (PIAS1) in HD mice and HD patient-derived induced pluripotent stem cells (iPSCs) and find a link between PIAS1 and DNA damage repair pathways. We show that PIAS1 is a component of the transcription-coupled repair complex, that includes the DNA damage end processing enzyme polynucleotide kinase-phosphatase (PNKP), and that PIAS1 is a SUMO E3 ligase for PNKP. Pias1 knockdown (KD) in HD mice had a normalizing effect on HD transcriptional dysregulation associated with synaptic function and disease-associated transcriptional coexpression modules enriched for DNA damage repair mechanisms as did reduction of PIAS1 in HD iPSC-derived neurons. KD also restored mutant HTT-perturbed enzymatic activity of PNKP and modulated genomic integrity of several transcriptionally normalized genes. The findings here now link SUMO modifying machinery to DNA damage repair responses and transcriptional modulation in neurodegenerative disease.

Indexed as

DNA RepairProtein Processing, Post-TranslationalAnimalsCell DifferentiationDisease Models, AnimalDNADNA DamageDNA Repair EnzymesFemaleHumansHuntingtin ProteinHuntington DiseaseMaleMiceMice, Inbred C57BLMice, TransgenicDNADNA Repair EnzymesHTT protein, humanHuntingtin ProteinPhosphotransferases (Alcohol Group Acceptor)PIAS1 protein, humanPNKP protein, humanProtein Inhibitors of Activated STATRNA, Small InterferingSmall Ubiquitin-Related Modifier ProteinsDNA damage repairHuntington's diseasePIASPNKPSUMO

Identifiers

PMID33468657
PMCPMC7848703
OpenAlexW3123631173

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.