Evidence map›Paper›PMID 16000378›Full record

ArticleMolecular biology of the cell2005

Calcium-activated RAF/MEK/ERK signaling pathway mediates p53-dependent apoptosis and is abrogated by alpha B-crystallin through inhibition of RAS activation.

David Wan-Cheng Li, Jin-Ping Liu, Ying-Wei Mao, Hua Xiang, Juan Wang, Wei-Ya Ma, Zigang Dong, Helen M Pike, Rhoderick E Brown, John C Reed

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

92 citing papers in PubMed, 176 citations in OpenAlex.

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  10. HSP90β prevents aging-related cataract formation through regulation of the charged multivesicular body protein (CHMP4B) and p53.Proceedings of the National Academy of Sciences of the United States of America · 2023
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32 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

10 authors at 6 institutions in 2 countries.

David Wan-Cheng LiHormel Institute, University of Minnesota, Austin, MN 55912, USA. dwcli@hi.umn.edu
Jin-Ping Liu
Ying-Wei Mao
Hua Xiang
Juan Wang
Wei-Ya Ma
Zigang Dong
Helen M Pike
Rhoderick E Brown
John C Reed
Hormel (United States) · USUniversity of Minnesota · USCalifornia University of Pennsylvania · USDiscovery Institute · USStratford University · USUniversity of Michigan–Ann Arbor · US

Funding

GLYCOLIPID TRANSFER--REGULATION BY MEMBRANE INTERFACESR01GM045928 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BROWN, RHODERICK E · 1992 to 2014
$4.8M
Antiapoptotic Mechanism of Protein Phosphatase-1 in LensR01EY015765 · NEI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI LI, DAVID W · 2005 to 2007
$873k
NEI NIH HHS EY 15765NEI NIH HHS R01 EY015765NIGMS NIH HHS R01 GM045928
6 · The paper itself

Abstract

The ocular lens is the only organ that does not develop spontaneous tumor. The molecular mechanism for this phenomenon remains unknown. Through examination of the signaling pathways mediating stress-induced apoptosis, here we presented evidence to show that different from most other tissues in which the extracellular signal-regulated kinases (ERKs) pathway is generally implicated in mediation of survival signals activated by different factors, the RAF/MEK/ERK signaling pathway alone plays a key role in stress-activated apoptosis of lens epithelial cells. Treatment of N/N1003A cells with calcimycin, a calcium mobilizer, activates the RAF/MEK/ERK pathway through RAS, which is indispensable for the induced apoptosis because inhibition of this pathway by either pharmacological drug or dominant negative mutants greatly attenuates the induced apoptosis. Calcimycin also activates p38 kinase and JNK2, which are not involved in calcium-induced apoptosis. Downstream of ERK activation, p53 is essential. Activation of RAF/MEK/ERK pathway by calcimycin leads to distinct up-regulation of p53. Moreover, overexpression of p53 enhances calcimycin-induced apoptosis, whereas inhibition of p53 expression attenuates calcimycin-induced apoptosis. Up-regulation of p53 directly promotes Bax expression, which changes the integrity of mitochondria, leading to release of cytochrome c, activation of caspase-3 and eventually execution of apoptosis. Overexpression of alphaB-crystallin, a member of the small heat-shock protein family, blocks activation of RAS to inhibit ERK1/2 activation, and greatly attenuates calcimycin-induced apoptosis. Together, our results provide 1) a partial explanation for the lack of spontaneous tumor in the lens, 2) a novel signaling pathway for calcium-induced apoptosis, and 3) a novel antiapoptotic mechanism for alphaB-crystallin.

Indexed as

alpha-Crystallin B ChainAnimalsApoptosisButadienesCalcimycinCalcium SignalingCaspase 3Caspase InhibitorsCell LineCytochromes cExtracellular Signal-Regulated MAP KinasesMAP Kinase Kinase Kinase 1MAP Kinase Kinase Kinase 2NitrilesRabbitsraf Kinasesalpha-Crystallin B ChainButadienesCalcimycinCaspase 3Caspase InhibitorsCytochromes cExtracellular Signal-Regulated MAP KinasesMAP Kinase Kinase Kinase 1MAP Kinase Kinase Kinase 2Nitrilesraf Kinasesras ProteinsTumor Suppressor Protein p53U 0126

Identifiers

PMID16000378
PMCPMC1196350
OpenAlexW2109072040

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.