Evidence map›Paper›PMID 25411248›Full record

ArticleThe Journal of biological chemistry2015

α-Actinin 4 potentiates nuclear factor κ-light-chain-enhancer of activated B-cell (NF-κB) activity in podocytes independent of its cytoplasmic actin binding function.

Xuan Zhao, Kuo-Sheng Hsu, Jun Hee Lim, Leslie A Bruggeman, Hung-Ying Kao

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

27 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
  2. Protein tyrosine phosphatase 1B is a regulator of alpha-actinin4 in the glomerular podocyte.Biochimica et biophysica acta. Molecular cell research · 2024
    Article
  3. Review
  4. Article
  5. Modeling ofKidney international reports · 2023
    Article
  6. Liver Proteome Alterations in Red Deer (Pathogens (Basel, Switzerland) · 2022
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Actinin-4 as a Diagnostic Biomarker in Serum of Breast Cancer Patients.Medical science monitor : international medical journal of experimental and clinical research · 2019
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. The Evolving Complexity of the Podocyte Cytoskeleton.Journal of the American Society of Nephrology : JASN · 2017
    Review
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

5 authors at 2 institutions in 1 country.

Xuan ZhaoFrom the Department of Biochemistry.
Kuo-Sheng HsuFrom the Department of Biochemistry.
Jun Hee LimFrom the Department of Biochemistry.
Leslie A BruggemanRammelkamp Center for Education and Research and Department of Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Hung-Ying KaoFrom the Department of Biochemistry, Case Comprehensive Cancer Center, and hxk43@cwru.edu.
Case Comprehensive Cancer CenterCase Western Reserve University · US

Funding

Alpha actinin 4: its functions and regulationR01DK078965 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI KAO, HUNG-YING · 2009 to 2013
$1.7M
Histone deacetylase 7 and its interacting proteins in endothelial cellsR01HL093269 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI KAO, HUNG-YING · 2010 to 2013
$1.5M
NHLBI NIH HHS HL093269NHLBI NIH HHS R01 HL093269NIDDK NIH HHS DK078965NIDDK NIH HHS R01 DK078965
6 · The paper itself

Abstract

Glomerular podocytes are highly specialized terminally differentiated cells that act as a filtration barrier in the kidney. Mutations in the actin-binding protein, α-actinin 4 (ACTN4), are linked to focal segmental glomerulosclerosis (FSGS), a chronic kidney disease characterized by proteinuria. Aberrant activation of NF-κB pathway in podocytes is implicated in glomerular diseases including proteinuria. We demonstrate here that stable knockdown of ACTN4 in podocytes significantly reduces TNFα-mediated induction of NF-κB target genes, including IL-1β and NPHS1, and activation of an NF-κB-driven reporter without interfering with p65 nuclear translocation. Overexpression of ACTN4 and an actin binding-defective variant increases the reporter activity. In contrast, an FSGS-linked ACTN4 mutant, K255E, which has increased actin binding activity and is predominantly cytoplasmic, fails to potentiate NF-κB activity. Mechanistically, IκBα blocks the association of ACTN4 and p65 in the cytosol. In response to TNFα, both NF-κB subunits p65 and p50 translocate to the nucleus, where they bind and recruit ACTN4 to their targeted promoters, IL-1β and IL-8. Taken together, our data identify ACTN4 as a novel coactivator for NF-κB transcription factors in podocytes. Importantly, this nuclear function of ACTN4 is independent of its actin binding activity in the cytoplasm.

Indexed as

Transcription, GeneticActininActinsAnimalsCell Line, TransformedGene Expression RegulationHEK293 CellsHeLa CellsHumansMaleMiceMice, Inbred C57BLNF-kappa BPodocytesProtein BindingRNA, Small InterferingActininActinsACTN4 protein, humanNF-kappa BRNA, Small InterferingACTN4Alpha-Actinin 4Focal Segmental GlomerulosclerosisFSGSGlomerulopathiesGlucocorticoid ReceptorNF-kappa B (NF-KB)PodocyteTranscriptional CoactivatorTranscription Regulation

Identifiers

PMID25411248
PMCPMC4281736
OpenAlexW2031289470

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.