Alpha-catulin, a Rho signalling component, can regulate NF-kappaB through binding to IKK-beta, and confers resistance to apoptosis.
Rho GTPases regulate diverse cellular functions including adhesion, cytokinesis and motility, as well as the activity of the transcription factors NF-kappaB, serum response factor and C/EBP. alpha-Catulin, an alpha-catenin-related protein that shares structural similarities with cytoskeletal linker proteins, facilitates Rho signalling by serving as a scaffold for the Rho-specific guanine nucleotide exchange factor Lbc. We report here that alpha-catulin also interacts with a key component of the NF-kappaB signalling pathway, namely the IkappaB kinase (IKK)-beta. In co-immunoprecipitations, alpha-catulin can bind IKK-beta and Lbc. Ectopic expression of alpha-catulin augmented NF-kappaB activity, promoted cell migration and increased resistance to apoptosis, whereas knockdown experiments showed the opposite effects. Together, these features suggest that alpha-catulin has tumorigenic potential.
Wiesner
C
C
Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
Winsauer
G
G
Resch
U
U
Hoeth
M
M
Schmid
J A
JA
van Hengel
J
J
van Roy
F
F
Binder
B R
BR
de Martin
R
R
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D019610:Cytoprotection / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D012234:Rho Factor / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
C495274:CTNNAL1 protein, human; D016895:Culture Media, Serum-Free; D018836:Inflammation Mediators; D016328:NF-kappa B; D012234:Rho Factor; D014409:Tumor Necrosis Factor-alpha; D051178:alpha Catenin; D051550:I-kappa B Kinase