Evidence map›Paper›PMID 33386492›Full record

ArticleApoptosis : an international journal on programmed cell death2021

Intracellular leucine-rich alpha-2-glycoprotein-1 competes with Apaf-1 for binding cytochrome c in protecting MCF-7 breast cancer cells from apoptosis.

Ronald Jemmerson, Katherine Staskus, LeeAnn Higgins, Kathleen Conklin, Ameeta Kelekar

Abstract read
In one paragraph

Article in Apoptosis : an international journal on programmed cell death, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
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

27 citing papers in PubMed.

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  11. Environmental and Genetic Determinants of Ankylosing Spondylitis.International journal of molecular sciences · 2024
    Review
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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

5 authors.

Ronald JemmersonDepartment of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA. jemme001@umn.edu.ORCID http://orcid.org/0000-0002-4288-7565
Katherine StaskusDepartment of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
LeeAnn HigginsDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
Kathleen ConklinDepartment of Genetics, Cell Biology, and Biophysics, Masonic Cancer Center, Minneapolis, MN, 55455, USA.
Ameeta KelekarDepartment of Laboratory Medicine and Pathology, Masonic Cancer Center, Minneapolis, MN, 55455, USA.

Funding

Role of a pro-apoptotic Bcl-2 protein in the survival and death of leukemia cellsR01CA157971 · NCI · UNIVERSITY OF MINNESOTA · PI KELEKAR, AMEETA · 2011 to 2015
$1.5M
NCI NIH HHS R01 CA157971
6 · The paper itself

Abstract

Leucine-rich alpha-2-glycoprotein-1 (LRG1) has been shown to compete with apoptosis activating factor-1 (Apaf-1) for binding cytochrome c (Cyt c) and could play a role in inhibition of apoptosis. Employing MCF-7 breast cancer cells, we report that intracellular LRG1 does protect against apoptosis. Thus, cells transfected with the lrg1 gene and expressing higher levels of LRG1 were more resistant to hydrogen peroxide-induced apoptosis than parental cells, while cells in which LRG mRNA was knocked down by short hairpin (sh) RNA-induced degradation were more sensitive. The amount of Cyt c co-immunoprecipitated with Apaf-1 from the cytosol of apoptotic cells was inversely related to the level of LRG1 expression. In lrg1-transfected cells partially-glycosylated LRG1 was found in the cytosol and there was an increase in cytosolic Cyt c in live lrg1-transfected cells relative to parental cells. However, apoptosis was not spontaneously induced because Cyt c was bound to LRG1 and not to Apaf-1. Cyt c was the only detectable protein co-immunoprecipitated with LRG1. Following hydrogen peroxide treatment degradation of LRG1 allowed for induction of apoptosis. We propose that intracellular LRG1 raises the threshold of cytoplasmic Cyt c required to induce apoptosis and, thus, prevents onset of the intrinsic pathway in cells where Cyt c release from mitochondria does not result from committed apoptotic signaling. This mechanism of survival afforded by LRG1 is likely to be distinct from its extracellular survival function that has been reported by several research groups.

Indexed as

ApoptosisApoptotic Protease-Activating Factor 1Breast NeoplasmsCytochromes cCytosolFemaleGlycoproteinsHumansMCF-7 CellsProtein BindingAPAF1 protein, humanApoptotic Protease-Activating Factor 1Cytochromes cGlycoproteinsLRG1 protein, humanApaf-1Cyt cLRG1MCF-7 cellsSurvival factor

Identifiers

PMID33386492
PMCPMC7904597

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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.