Evidence map›Paper›PMID 23319048›Full record

ArticleMolecular and cellular biology2013

SCO2 induces p53-mediated apoptosis by Thr845 phosphorylation of ASK-1 and dissociation of the ASK-1-Trx complex.

Esha Madan, Rajan Gogna, Periannan Kuppusamy, Madan Bhatt, Abbas Ali Mahdi, Uttam Pati

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

Article in Molecular and cellular biology, 2013. 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
1.3field-weighted citation impact, top 19% 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

27 citing papers in PubMed, 47 citations in OpenAlex.

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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

6 authors at 3 institutions in 2 countries.

Esha MadanDepartment of Biochemistry, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India.
Rajan Gogna
Periannan Kuppusamy
Madan Bhatt
Abbas Ali Mahdi
Uttam Pati
Jawaharlal Nehru University · INKing George's Medical University · INThe Ohio State University · US

Funding

Probes and Methods for Clinical OximetryR01EB004031 · NIBIB · OHIO STATE UNIVERSITY · PI KUPPUSAMY, PERIANNAN · 2004 to 2021
$7.1M
NIBIB NIH HHS R01 EB004031NIBIB NIH HHS R01EB004031
6 · The paper itself

Abstract

p53 prevents cancer via cell cycle arrest, apoptosis, and the maintenance of genome stability. p53 also regulates energy-generating metabolic pathways such as oxidative phosphorylation (OXPHOS) and glycolysis via transcriptional regulation of SCO2 and TIGAR. SCO2, a cytochrome c oxidase assembly factor, is a metallochaperone which is involved in the biogenesis of cytochrome c oxidase subunit II. Here we have shown that SCO2 functions as an apoptotic protein in tumor xenografts, thus providing an alternative pathway for p53-mediated apoptosis. SCO2 increases the generation of reactive oxygen species (ROS) and induces dissociation of the protein complex between apoptosis signal-regulating kinase 1 (ASK-1) (mitogen-activated protein kinase kinase kinase [MAPKKK]) and its cellular inhibitor, the redox-active protein thioredoxin (Trx). Furthermore, SCO2 induces phosphorylation of ASK-1 at the Thr(845) residue, resulting in the activation of the ASK-1 kinase pathway. The phosphorylation of ASK-1 induces the activation of mitogen-activated protein kinase kinases 4 and 7 (MAP2K4/7) and MAP2K3/6, which switches the c-Jun N-terminal protein kinase (JNK)/p38-dependent apoptotic cascades in cancer cells. Exogenous addition of the SCO2 gene to hypoxic cancer cells and hypoxic tumors induces apoptosis and causes significant regression of tumor xenografts. We have thus discovered a novel apoptotic function of SCO2, which activates the ASK-1 kinase pathway in switching "on" an alternate mode of p53-mediated apoptosis. We propose that SCO2 might possess a novel tumor suppressor function via the ROS-ASK-1 kinase pathway and thus could be an important candidate for anticancer gene therapy.

Indexed as

ApoptosisCarrier ProteinsCell Line, TumorHumansIntracellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesMAP Kinase Kinase Kinase 5MCF-7 CellsMembrane ProteinsMitochondrial ProteinsMitogen-Activated Protein Kinase KinasesMolecular Chaperonesp38 Mitogen-Activated Protein KinasesPhosphorylationReactive Oxygen SpeciesSignal TransductionCarrier ProteinsIntracellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesMAP3K5 protein, humanMAP Kinase Kinase Kinase 5Membrane ProteinsMitochondrial ProteinsMitogen-Activated Protein Kinase KinasesMolecular Chaperonesp38 Mitogen-Activated Protein KinasesReactive Oxygen SpeciesSCO2 protein, humanTP53 protein, humanTumor Suppressor Protein p53VAC14 protein, human

Identifiers

PMID23319048
PMCPMC3624269
OpenAlexW2167575664

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.