Evidence map›Paper›PMID 20571027›Full record

ArticleThe Journal of biological chemistry2010

Mechanism of regulation of bcl-2 mRNA by nucleolin and A+U-rich element-binding factor 1 (AUF1).

Daniella Ishimaru, Lisa Zuraw, Sivakumar Ramalingam, Tapas K Sengupta, Sumita Bandyopadhyay, Adrian Reuben, Daniel J Fernandes, Eleanor K Spicer

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 2 pooled it
4.3field-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

69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 114 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Nucleolin Alterations and ROS Production Associate With Sensitivity of AML Cells to Venetoclax.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. The RGG motif proteins: Interactions, functions, and regulations.Wiley interdisciplinary reviews. RNA · 2023
    Review
  13. Anti-nucleolin aptamer AS1411: an advancing therapeutic.Frontiers in molecular biosciences · 2023
    Review
  14. RNA binding proteins in MLL-rearranged leukemia.Experimental hematology & oncology · 2022
    Review
  15. Article
  16. Article
  17. Review
  18. RNA binding proteins in osteoarthritis.Frontiers in cell and developmental biology · 2022
    Review
  19. Article
  20. Article

9 more citing papers are in PubMed but not listed here.

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.

Daniella IshimaruDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425.
Lisa ZurawDepartment of Chemistry, The Citadel, Charleston, South Carolina 29409.
Sivakumar RamalingamDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425.
Tapas K SenguptaDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425.
Sumita BandyopadhyayDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425.
Adrian ReubenDivision of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425.
Daniel J FernandesDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425.
Eleanor K SpicerDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425. Electronic address: spicer@musc.edu.
Medical University of South Carolina · USCitadel · US

Funding

Drug-Induced Destabilization of Bcl-2 mRNAR01CA109254 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI FERNANDES, DANIEL J · 2005 to 2009
$1.1M
Post-transcription regulation of human bcl-2 expressionR01CA087553 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI SPICER, ELEANOR K · 2002 to 2005
$832k
NCI NIH HHS CA109254NCI NIH HHS CA 87553NCI NIH HHS R01 CA087553NCI NIH HHS R01 CA109254
6 · The paper itself

Abstract

The antiapoptotic Bcl-2 protein is overexpressed in a variety of cancers, particularly leukemias. In some cell types this is the result of enhanced stability of bcl-2 mRNA, which is controlled by elements in its 3'-untranslated region. Nucleolin is one of the proteins that binds to bcl-2 mRNA, thereby increasing its half-life. Here, we examined the site on the bcl-2 3'-untranslated region that is bound by nucleolin as well as the protein binding domains important for bcl-2 mRNA recognition. RNase footprinting and RNA fragment binding assays demonstrated that nucleolin binds to a 40-nucleotide region at the 5' end of the 136-nucleotide bcl-2 AU-rich element (ARE(bcl-2)). The first two RNA binding domains of nucleolin were sufficient for high affinity binding to ARE(bcl-2). In RNA decay assays, ARE(bcl-2) transcripts were protected from exosomal decay by the addition of nucleolin. AUF1 has been shown to recruit the exosome to mRNAs. When MV-4-11 cell extracts were immunodepleted of AUF1, the rate of decay of ARE(bcl-2) transcripts was reduced, indicating that nucleolin and AUF1 have opposing roles in bcl-2 mRNA turnover. When the function of nucleolin in MV-4-11 cells was impaired by treatment with the nucleolin-targeting aptamer AS1411, association of AUF1 with bcl-2 mRNA was increased. This suggests that the degradation of bcl-2 mRNA induced by AS1411 results from both interference with nucleolin protection of bcl-2 mRNA and recruitment of the exosome by AUF1. Based on our findings, we propose a model that illustrates the opposing roles of nucleolin and AUF1 in regulating bcl-2 mRNA stability.

Indexed as

3' Untranslated RegionsModels, BiologicalAptamers, NucleotideHeLa CellsHeterogeneous-Nuclear Ribonucleoprotein DHeterogeneous Nuclear Ribonucleoprotein D0HumansLeukemiaNucleolinOligodeoxyribonucleotidesPhosphoproteinsProtein BindingProtein Structure, TertiaryProto-Oncogene Proteins c-bcl-2RNA-Binding ProteinsRNA, Neoplasm3' Untranslated RegionsAGRO 100Aptamers, NucleotideHeterogeneous-Nuclear Ribonucleoprotein DHeterogeneous Nuclear Ribonucleoprotein D0HNRNPD protein, humanNucleolinOligodeoxyribonucleotidesPhosphoproteinsProto-Oncogene Proteins c-bcl-2RNA-Binding ProteinsRNA, Neoplasm

Identifiers

PMID20571027
PMCPMC2930717
OpenAlexW2063986949

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.