Evidence map›Paper›PMID 17379600›Full record

ArticleThe Journal of biological chemistry2007

Effect of inositol hexakisphosphate kinase 2 on transforming growth factor beta-activated kinase 1 and NF-kappaB activation.

Bei H Morrison, Joseph A Bauer, Joseph A Lupica, Zhuo Tang, Heidi Szugye, Joseph A DiDonato, Daniel J Lindner

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

Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-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

13 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. The Key Role of IPMolecules (Basel, Switzerland) · 2020
    Review
  3. Review
  4. Article
  5. The inositol pyrophosphate pathway in health and diseases.Biological reviews of the Cambridge Philosophical Society · 2018
    Review
  6. Article
  7. Review
  8. Review
  9. Casein kinase-2 mediates cell survival through phosphorylation and degradation of inositol hexakisphosphate kinase-2.Proceedings of the National Academy of Sciences of the United States of America · 2011
    Article
  10. Inositol pyrophosphates: structure, enzymology and function.Cellular and molecular life sciences : CMLS · 2009
    Review
  11. Review
  12. IP6K2 is a client for HSP90 and a target for cancer therapeutics development.Proceedings of the National Academy of Sciences of the United States of America · 2008
    Article
  13. HSP90 regulates cell survival via inositol hexakisphosphate kinase-2.Proceedings of the National Academy of Sciences of the United States of America · 2008
    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.

Bei H MorrisonCenter for Hematology and Oncology Molecular Therapeutics, Taussig Cancer Center, and Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Joseph A Bauer
Joseph A Lupica
Zhuo Tang
Heidi Szugye
Joseph A DiDonato
Daniel J Lindner
Cleveland Clinic · USCleveland Clinic Lerner College of Medicine · US

Funding

Inositol hexakisphosphate kinase 2:apoptosis regulatorR01CA095020 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LINDNER, DANIEL J · 2003 to 2006
$1.1M
NCI NIH HHS CA095020NCI NIH HHS R01 CA095020
6 · The paper itself

Abstract

We previously showed that inositol hexakisphosphate kinase 2 (IHPK2) functions as a growth-suppressive and apoptosis-enhancing kinase during cell stress. Overexpression of IHPK2 sensitized ovarian carcinoma cell lines to the growth-suppressive and apoptotic effects of interferon beta (IFN-beta), IFN-alpha2, and gamma-irradiation. Expression of a kinase-dead mutant abrogated 50% of the apoptosis induced by IFN-beta. Because the kinase-dead mutant retained significant response to cell stressors, we hypothesized that a portion of the death-promoting function of IHPK2 was independent of its kinase activity. We now demonstrate that IHPK2 binds to tumor necrosis factor (TNF) receptor-associated factor (TRAF) 2 and interferes with phosphorylation of transforming growth factor beta-activated kinase 1 (TAK1), thereby inhibiting NF-kappaB signaling. IHPK2 contains two sites required for TRAF2 binding, Ser-347 and Ser-359. Compared with wild type IHPK2-transfected cells, cells expressing S347A and S359A mutations displayed 3.5-fold greater TAK1 activation following TNF-alpha. This mutant demonstrated a 6-10-fold increase in NF-kappaB DNA binding following TNF-alpha compared with wild type IHPK2-expressing cells in which NF-kappaB DNA binding was inhibited. Cells transfected with wild type IHPK2 or IHPK2 mutants that lacked S347A and S359A mutations displayed enhanced terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling staining following TNF-alpha. We believe that IHPK2-TRAF2 binding leads to attenuation of TAK1- and NF-kappaB-mediated signaling and is partially responsible for the apoptotic activity of IHPK2.

Indexed as

ApoptosisMAP Kinase Signaling SystemAmino Acid SubstitutionAnimalsCell Line, TumorGamma RaysGene ExpressionHumansInterferon-alphaInterferon-betaMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMiceMutation, MissenseNF-kappa BPhosphotransferases (Phosphate Group Acceptor)inositol hexakisphosphate kinaseInterferon-alphaInterferon-betaMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesNF-kappa BPhosphotransferases (Phosphate Group Acceptor)TNF Receptor-Associated Factor 2

Identifiers

PMID17379600
PMCPMC2048714
OpenAlexW2019960866

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.