Evidence map›Paper›PMID 26972597›Full record

ArticleScientific reports2016

FADD regulates NF-κB activation and promotes ubiquitination of cFLIPL to induce apoptosis.

Kishu Ranjan, Chandramani Pathak

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

31 citing papers in PubMed, 53 citations in OpenAlex.

  1. Review
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  4. NLRP inflammasomes in health and disease.Molecular biomedicine · 2024
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  9. Insights of Endocytosis Signaling in Health and Disease.International journal of molecular sciences · 2023
    Review
  10. Article
  11. Article
  12. A Dual Role for FADD in Human Precursor T-Cell Neoplasms.International journal of molecular sciences · 2022
    Article
  13. Review
  14. FADD as a key molecular player in cancer progression.Molecular medicine (Cambridge, Mass.) · 2022
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. 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

2 authors at 1 institution in 1 country.

Kishu RanjanDepartment of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Koba Institutional Area, Gandhinagar-382007, Gujarat, India.
Chandramani PathakDepartment of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Koba Institutional Area, Gandhinagar-382007, Gujarat, India.
Indian Institute of Advanced Research · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor Necrosis Factor-α canonically induces the activation of NF-κB and associated gene product cellular FLICE-like inhibitory protein (cFLIPL) to promote cell survival. Previously, we demonstrated that ectopic expression of the Fas associated death domain (FADD) diminishes the expression of cFLIPL and transduces caspases-8 mediated apoptosis, independent of FasL stimulation in HEK 293T cells. However, the underlying molecular mechanism of FADD mediated ablation of cFLIP and NF-κB signaling to determining the fate of cell death or survival remains elusive. Here, we explored a novel molecular mechanism of FADD mediated apoptotic cell death that was directed by ubiquitination of cFLIPL and inhibition of NF-κB activation, independent of TNF-α stimulation. We found that induced expression of FADD firmly interacts with procaspase-8 and precludes cFLIPL to from the death inducing signaling complex (DISC). In addition, FADD negatively regulates cellular inhibitor of apoptosis protein 2 (cIAP2) and Bcl-2. Furthermore, FADD restrains cIAP2 expression and interacts with RIP1 and procaspase-8 to accomplish apoptotic cell death signaling. Interestingly, FADD was also found to promote JNK1 mediated activation of E3 ubiquitin ligase ITCH to degrade cFLIPL that may lead to commencement of apoptosis. Thus, FADD is an important regulator for determining the fate of cell death or survival.

Indexed as

ApoptosisUbiquitinationA549 CellsAnimalsBaculoviral IAP Repeat-Containing 3 ProteinBlotting, WesternCASP8 and FADD-Like Apoptosis Regulating ProteinCaspase 8Cell LineCell SurvivalFas-Associated Death Domain ProteinHCT116 CellsHEK293 CellsHeLa CellsHT29 CellsHumansBaculoviral IAP Repeat-Containing 3 ProteinBIRC3 protein, humanCASP8 and FADD-Like Apoptosis Regulating ProteinCaspase 8CFLAR protein, humanFADD protein, humanFas-Associated Death Domain ProteinInhibitor of Apoptosis ProteinsITCH protein, humanNF-kappa BRepressor ProteinsTumor Necrosis Factor-alphaUbiquitin-Protein Ligases

Identifiers

PMID26972597
PMCPMC4789601
OpenAlexW2298375517

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Registered trials

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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.