SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Mercurio Valentina)
 

Sökning: WFRF:(Mercurio Valentina) > (2003-2004) > Transient activatio...

  • Arsura, Marcello (författare)

Transient activation of NF-kappaB through a TAK1/IKK kinase pathway by TGF-beta1 inhibits AP-1/SMAD signaling and apoptosis : implications in liver tumor formation.

  • Artikel/kapitelEngelska2003

Förlag, utgivningsår, omfång ...

  • 2003-01-22
  • Springer Science and Business Media LLC,2003
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-10478
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-10478URI
  • https://doi.org/10.1038/sj.onc.1206132DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • NF-kappaB has been implicated in the regulation of apoptosis, a key mechanism of normal and malignant growth control. Previously, we demonstrated that inhibition of NF-kappaB activity by TGF-beta1 leads directly to induction of apoptosis of murine B-cell lymphomas and hepatocytes. Thus, we were surprised to determine that NF-kappaB is transiently activated in response to TGF-beta1 treatment. Here we elucidate the mechanism of TGF-beta1-mediated regulation of NF-kappaB and induction of apoptosis in epithelial cells. We report that TGF-beta1 activates IKK kinase, which mediates IkappaB-alpha phosphorylation. In turn, the activation of IKK following TGF-beta1 treatment is mediated by the TAK1 kinase. As a result of NF-kappaB activation, IkappaB-alpha mRNA and protein levels are increased leading to postrepression of NF-kappaB and induction of cell death. Inhibition of NF-kappaB following TGF-beta1 treatment increased AP-1 complex transcriptional activity through sustained c-Jun phosphorylation, thereby potentiating AP-1/SMADs-mediated cell killing. Furthermore, TGF-beta1-mediated upregulation of Smad7 appeared independent of NF-kappaB. In hepatocellular carcinomas of TGF-beta1 or TGF-alpha/c-myc transgenic mice, we observed constitutive activation of NF-kappaB that led to inhibition of JNK signaling. Overall, our data illustrate an autocrine mechanism based on the ability of IKK/NF-kappaB/IkappaB-alpha signaling to negatively regulate NF-kappaB levels thereby permitting TGF-beta1-induced apoptosis through AP-1 activity.

Ämnesord och genrebeteckningar

  • Animals
  • Apoptosis/drug effects/physiology
  • Carcinoma; Hepatocellular/genetics/metabolism/pathology
  • Cells; Cultured
  • DNA-Binding Proteins/genetics/*metabolism
  • Enzyme Activation
  • Hepatocytes/cytology/metabolism
  • I-kappa B Kinase
  • I-kappa B Proteins/metabolism
  • JNK Mitogen-Activated Protein Kinases
  • Liver Neoplasms/genetics/metabolism/pathology
  • MAP Kinase Kinase Kinases/genetics/*metabolism
  • Mice
  • Mice; Transgenic
  • Mitogen-Activated Protein Kinases/metabolism
  • NF-kappa B/genetics/*metabolism
  • Phosphorylation
  • Protein Transport/drug effects
  • Protein-Serine-Threonine Kinases/genetics/*metabolism
  • Proto-Oncogene Proteins c-myc/genetics/metabolism
  • Signal Transduction
  • Smad7 Protein
  • Trans-Activators/genetics/*metabolism
  • Transcription Factor AP-1/*metabolism
  • Transforming Growth Factor beta/*metabolism/pharmacology
  • Transforming Growth Factor beta1

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Panta, Ganesh R. (författare)
  • Bilyeu, Jennifer D. (författare)
  • Cavin, Lakita G. (författare)
  • Sovak, Mika A. (författare)
  • Oliver, Aundrea A. (författare)
  • Factor, Valentina (författare)
  • Heuchel, RainerUppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)rainheuc (författare)
  • Mercurio, Frank (författare)
  • Thorgeirsson, Snorri S. (författare)
  • Sonenshein, Gail E. (författare)
  • Uppsala universitetLudwiginstitutet för cancerforskning (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Oncogene: Springer Science and Business Media LLC22:3, s. 412-4250950-92321476-5594

Internetlänk

Hitta via bibliotek

  • Oncogene (Sök värdpublikationen i LIBRIS)

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy