Evidence map›Paper›PMID 24330068›Full record

ArticleThe FEBS journal2014

Nuclear Raf-1 kinase regulates the CXCR5 promoter by associating with NFATc3 to drive retinoic acid-induced leukemic cell differentiation.

Wendy M Geil, Andrew Yen

Abstract read
In one paragraph

Article in The FEBS journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

20 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. CXCL13 Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021
    Review
  7. Article
  8. Article
  9. Roscovitine enhances all-Oncotarget · 2020
    Article
  10. Article
  11. Article
  12. Nuclear localized Raf1 isoform alters DNA-dependent protein kinase activity and the DNA damage response.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Retinoid Chemoprevention: Who Can Benefit?Current pharmacology reports · 2015
    Article
  18. Article
  19. Article
  20. Article
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.

Wendy M GeilDepartment of Biomedical Sciences, Cornell University, Ithaca, NY, USA.
Andrew Yen
Cornell University · US

Funding

TRANS-NETWORK PROJECTSU54CA143876 · NCI · CORNELL UNIVERSITY · PI SHULER, MICHAEL L · 2009 to 2014
$12.6M
NUTRITIONAL CELL CYCLE AND DIFFERENTIATION CONTROLR01CA033505 · NCI · UNIVERSITY OF IOWA · PI YEN, ANDREW · 1985 to 2013
$3.2M
Mechanism of Action of Retinoic Acid Using CD38R01CA152870 · NCI · CORNELL UNIVERSITY · PI HAO, QUAN, LIN, HENING · 2011 to 2015
$1.6M
NCI NIH HHS R01 CA033505NCI NIH HHS R01 CA152870NCI NIH HHS U54 CA143876
6 · The paper itself

Abstract

Novel functions of signaling molecules have been revealed in studies of cancer stem cells. Retinoic acid (RA) is an embryonic morphogen and stem cell regulator that controls the differentiation of a patient-derived leukemic cell line, HL-60, which is composed of progenitor cells with bipotent myelo-monocytic differentiation capability. RA treatment of HL-60 cells causes unusually long-lasting mitogen-activated protein kinase signaling, with the cells exhibiting the beginning of G0 cell cycle arrest and functional differentiation by 48 h after treatment with RA. This event coincides with the nuclear translocation of Raf-1, phosphorylated at serine 621. The present study shows how the novel localization of Raf-1 to the nucleus results in transcriptional changes that contribute to the differentiation of HL-60 cells induced by RA. We find that nuclear pS621 Raf-1 associates with NFATc3 near its cognate binding site in the promoter of CXCR5, a gene that must be up-regulated to drive RA-induced differentiation. NFATc3 becomes immunoprecipitable with anti-phosphoserine serum, and CXCR5 is transcriptionally up-regulated upon RA-induced differentiation. Inhibiting the pS621 Raf-1/NFATc3 association with PD98059 inhibits these processes and cripples RA-induced differentiation. In this novel paradigm for Raf-1 and RA function, Raf-1 has a role in driving the nuclear signaling of RA-induced differentiation of leukemic progenitor cells.

Indexed as

Cell DifferentiationFlavonoidsHL-60 CellsHumansNFATC Transcription FactorsPhosphorylationPromoter Regions, GeneticProto-Oncogene Proteins c-rafReceptors, CXCR5Tretinoin2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-oneCXCR5 protein, humanFlavonoidsNFATC3 protein, humanNFATC Transcription FactorsProto-Oncogene Proteins c-rafReceptors, CXCR5TretinoinCXCR5differentiationNFATc3Raf-1retinoic acid

Identifiers

PMID24330068
PMCPMC4057990
OpenAlexW2043859776

What OpenQuestion holds

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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.