Sökning: onr:"swepub:oai:DiVA.org:uu-10478" >
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
- Av författaren/redakt...
-
Arsura, Marcello
-
Panta, Ganesh R.
-
Bilyeu, Jennifer ...
-
Cavin, Lakita G.
-
Sovak, Mika A.
-
Oliver, Aundrea ...
-
visa fler...
-
Factor, Valentin ...
-
Heuchel, Rainer
-
Mercurio, Frank
-
Thorgeirsson, Sn ...
-
Sonenshein, Gail ...
-
visa färre...
- Artiklar i publikationen
-
Oncogene
- Av lärosätet
-
Uppsala universitet