NF-kappaB activation in cancer: a challenge for ubiquitination- and proteasome-based therapeutic approach

Semin Cancer Biol. 2003 Feb;13(1):15-28. doi: 10.1016/s1044-579x(02)00096-2.

Abstract

Nuclear factor-kappa B (NF-kappaB) activation relies primarily on ubiquitin-mediated degradation of its inhibitor IkappaB. NF-kappaB plays an important role in many aspects of tumor development, progression, and therapy. Some types of cancer are characterized by constitutive NF-kappaB activity, whereas in others such activity is induced following chemotherapy. NF-kappaB-harboring tumors are generally resistant to chemotherapy and their eradication requires NF-kappaB inhibition. Here we describe the mechanisms of NF-kappaB activation in normal and tumor cells, review prevalent notions regarding the factor's contribution to tumorigenicity and discuss present and future options for NF-kappaB inhibition in cancer. The ubiquitination-mediated activation of NF-kappaB is intersected by another cancer-associated protein, beta-catenin. We, therefore, compare the related activation pathways and discuss the possibility of differential targeting of the involved ubiquitination machinery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cysteine Endopeptidases / metabolism
  • Cysteine Endopeptidases / therapeutic use*
  • Cytoskeletal Proteins / metabolism
  • Female
  • Hodgkin Disease / metabolism
  • Humans
  • Male
  • Multienzyme Complexes / metabolism
  • Multienzyme Complexes / therapeutic use*
  • NF-kappa B / metabolism*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Proteasome Endopeptidase Complex
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Structure, Tertiary
  • Receptors, Steroid / metabolism
  • Trans-Activators / metabolism
  • Ubiquitins / metabolism*
  • Ubiquitins / therapeutic use
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Multienzyme Complexes
  • NF-kappa B
  • Receptors, Steroid
  • Trans-Activators
  • Ubiquitins
  • beta Catenin
  • Protein Serine-Threonine Kinases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex