Evidence map›Paper›PMID 21364639›Full record

ArticleCell death & disease2010

The anti-apoptotic function of human αA-crystallin is directly related to its chaperone activity.

N Pasupuleti, S Matsuyama, O Voss, A I Doseff, K Song, D Danielpour, R H Nagaraj

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

56 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
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  9. Article
  10. Mini-Journal of ophthalmology · 2023
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  13. Small Heat Shock Proteins in Retinal Diseases.Frontiers in molecular biosciences · 2022
    Review
  14. Review
  15. Article
  16. Article
  17. Effect of Structural Changes Induced by Deletion ofInternational journal of molecular sciences · 2021
    Article
  18. Review
  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

7 authors at 2 institutions in 1 country.

N PasupuletiDepartment of Ophthalmology and Visual Sciences, Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
S Matsuyama
O Voss
A I Doseff
K Song
D Danielpour
R H Nagaraj
Case Western Reserve University · USThe Ohio State University · US

Funding

TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7M
MAILLARD REACTIONS AND OXIDATION IN CATARACTOGENESISR01EY009912 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI NAGARAJ, RAM H · 1998 to 2012
$3.1M
Modifications of Small Heat Shock Proteins in the LensR01EY016219 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI NAGARAJ, RAM H · 2005 to 2009
$1.9M
Molecular Mechanisms of Apoptosis in MonocytesR01HL075040 · NHLBI · OHIO STATE UNIVERSITY · PI DOSEFF, ANDREA · 2006 to 2010
$1.9M
Androgen Control of TGF-beta signalingR01CA102074 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI DANIELPOUR, DAVID · 2004 to 2008
$1.5M
Bax Activation Mechanism in the CytosolR01AG031903 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI MATSUYAMA, SHIGEMI · 2008 to 2012
$1.4M
NCI NIH HHS R01 CA102074NCI NIH HHS R01CA102074NEI NIH HHS P30 EY011373NEI NIH HHS P30EY11373NEI NIH HHS R01 EY009912NEI NIH HHS R01 EY016219NEI NIH HHS R01EY-016219NEI NIH HHS R01EY-09912NHLBI NIH HHS R01 HL075040NHLBI NIH HHS R01HL075040-01NIA NIH HHS R01 AG031903NIA NIH HHS R01AG031903
6 · The paper itself

Abstract

αA-crystallin is a molecular chaperone and an antiapoptotic protein. This study investigated the mechanism of inhibition of apoptosis by human αA-crystallin and determined if the chaperone activity of αA-crystallin is required for the antiapoptotic function. αA-crystallin inhibited chemical-induced apoptosis in Chinese hamster ovary (CHO) cells and HeLa cells by inhibiting activation of caspase-3 and -9. In CHO cells, it inhibited apoptosis induced by the overexpression of human proapoptotic proteins, Bim and Bax. αA-crystallin inhibited doxorubicin-mediated activation of human procaspase-3 in CHO cells and it activated the PI3K/Akt cell survival pathway by promoting the phosphorylation of PDK1, Akt and phosphatase tensin homologue in HeLa cells. The phosphoinositide 3 kinase (PI3K) activity was increased by αA-crystallin overexpression but the protein content was unaltered. Downregulation of PI3K by the expression of a dominant-negative mutant or inhibition by LY294002 abrogated the ability of αA-crystallin to phosphorylate Akt. These antiapoptotic functions of αA-crystallin were enhanced in a mutant protein (R21A) that shows increased chaperone activity than the wild-type (Wt) protein. Interestingly, a mutant protein (R49A) that shows decreased chaperone activity was far weaker than the Wt protein in its antiapoptotic functions. Together, our study results show that αA-crystallin inhibits apoptosis by enhancing PI3K activity and inactivating phosphatase tensin homologue and that the antiapoptotic function is directly related to its chaperone activity.

Indexed as

AnimalsApoptosisApoptosis Regulatory Proteinsbcl-2-Associated X ProteinBcl-2-Like Protein 11Caspase 3Caspase 9Caspase InhibitorsCHO CellsCricetinaeCricetulusCrystallinsCytochromes cDoxorubicinEnzyme ActivationEnzyme InhibitorsApoptosis Regulatory Proteinsbcl-2-Associated X ProteinBCL2L11 protein, humanBcl-2-Like Protein 11Caspase 3Caspase 9Caspase InhibitorsCRYAA protein, humanCrystallinsCytochromes cDoxorubicinEnzyme InhibitorsMembrane ProteinsPDK1 protein, humanPhosphatidylinositol 3-KinaseProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePTEN protein, humanPyruvate Dehydrogenase Acetyl-Transferring Kinase

Identifiers

PMID21364639
PMCPMC3032290
OpenAlexW1975344225

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.