RGD Reference Report - Sustained activation of protein kinase C downregulates nuclear factor-kappaB signaling by dissociation of IKK-gamma and Hsp90 complex in human colonic epithelial cells. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Sustained activation of protein kinase C downregulates nuclear factor-kappaB signaling by dissociation of IKK-gamma and Hsp90 complex in human colonic epithelial cells.

Authors: Park, Kyeong Ah  Byun, Hee Sun  Won, Minho  Yang, Keum-Jin  Shin, Sanghee  Piao, Longzhen  Kim, Jin Man  Yoon, Wan-Hee  Junn, Eunsung  Park, Jongsun  Seok, Jeong Ho  Hur, Gang Min 
Citation: Park KA, etal., Carcinogenesis. 2007 Jan;28(1):71-80. doi: 10.1093/carcin/bgl094. Epub 2006 Jun 14.
RGD ID: 153305944
Pubmed: PMID:16774932   (View Abstract at PubMed)
DOI: DOI:10.1093/carcin/bgl094   (Journal Full-text)

Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) triggers cellular signals that lead to the activation of the transcription factor NF-kappaB (nuclear factor kappaB) in various cell types. In addition to NF-kappaB activation by short-time PMA treatment, here we report that the prolonged exposure of human colonic cancer epithelial cells treated with PMA can also lead to a persistent inhibition of NF-kappaB activation. PMA selectively causes the degradation of IkappaB kinases (IKKs) including IKK-gamma and IKK-beta, and subsequent inhibition of tumor necrosis factor (TNF) induced IKK and NF-kappaB activation in human colon cancer cell line HCT-116, but not in other gastrointestinal tract cells. The use of Ro-318220 and GO-6983, general PKC inhibitors as well as MG-132, a proteasome-specific inhibitor, abrogated PMA-induced degradation of IKK-gamma and recovered the activation of IKK by TNF, suggesting that IKK complex is predominantly degraded by the proteasome pathway in a PKC-dependent manner. We also found that IKK-gamma strongly associates with heat shock protein 90 (Hsp90) in HCT-116 cells, and that this interaction was dramatically reduced after exposure to PMA. Furthermore, high levels of Hsp90 expression and enhanced association with IKK were observed in human colon cancer tissues. Taken together, these results suggest that long-term activation of PKC by PMA inhibits NF-kappaB system in case of colon cancer cells by disrupting the interaction of IKK-gamma with Hsp90, which may represent a novel regulatory mechanism of PKC-dependent cellular differentiation and limited proliferation of colonic epithelial cells.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CHUKHumancolon cancer  IEP protein:increased expression:colon (human)RGD 
ChukRatcolon cancer  ISOCHUK (Homo sapiens)protein:increased expression:colon (human)RGD 
ChukMousecolon cancer  ISOCHUK (Homo sapiens)protein:increased expression:colon (human)RGD 
HSP90AA1Humancolon cancer  IEP protein:increased expression:colon (human)RGD 
Hsp90aa1Ratcolon cancer  ISOHSP90AA1 (Homo sapiens)protein:increased expression:colon (human)RGD 
Hsp90aa1Mousecolon cancer  ISOHSP90AA1 (Homo sapiens)protein:increased expression:colon (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Chuk  (component of inhibitor of nuclear factor kappa B kinase complex)
Hsp90aa1  (heat shock protein 90 alpha family class A member 1)

Genes (Mus musculus)
Chuk  (conserved helix-loop-helix ubiquitous kinase)
Hsp90aa1  (heat shock protein 90, alpha (cytosolic), class A member 1)

Genes (Homo sapiens)
CHUK  (component of inhibitor of nuclear factor kappa B kinase complex)
HSP90AA1  (heat shock protein 90 alpha family class A member 1)


Additional Information