Alpha-catulin, a Rho signalling component, can regulate NF-kappaB through binding to IKK-beta, and confers resistance to apoptosis

Oncogene. 2008 Apr 3;27(15):2159-69. doi: 10.1038/sj.onc.1210863. Epub 2007 Oct 22.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Cell Movement / genetics
  • Cells, Cultured
  • Culture Media, Serum-Free / pharmacology
  • Cytoprotection / genetics
  • HeLa Cells
  • Humans
  • I-kappa B Kinase / metabolism*
  • Inflammation Mediators / metabolism
  • NF-kappa B / metabolism*
  • Protein Binding
  • Rho Factor / metabolism
  • Rho Factor / physiology
  • Signal Transduction / physiology
  • Tissue Distribution
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology
  • alpha Catenin / genetics
  • alpha Catenin / metabolism*
  • alpha Catenin / physiology*

Substances

  • CTNNAL1 protein, human
  • Culture Media, Serum-Free
  • Inflammation Mediators
  • NF-kappa B
  • Rho Factor
  • Tumor Necrosis Factor-alpha
  • alpha Catenin
  • I-kappa B Kinase