Regulation of NF-kB in multiple myeloma: therapeutic implications.
The nuclear factor kappa B (NF-kappaB) family of transcription factors plays a major role in inflammation, immune and stress responses, oncogenesis, cell migration, and angiogenesis. Aberrant activation of NF-kappaB has also been shown to contribute to intrinsic and inducible drug resistance in numerous cancers, including multiple myeloma. The expression of NF-kappaB-responsive targets will vary depending on the cellular context and type of inducer. The regulation of NF-kappaB activity occurs at multiple levels involving the IkappaB kinase (IKK) complex, members of the IkappaB family, recruitment of heterologous transcription factors and coactivators by NF-kappaB, and post-translational modifications of p65. This article highlights regulatory mechanisms responsible for constitutive NF-kappaB activation and provides justification for target-based therapy for NF-kappaB in multiple myeloma.
Feinman
Rena
R
Department of Surgery, UMDNJ-New Jersey Medical School, 185 South Orange Avenue MSB-G510, Newark, NJ 07103, USA. feinmarr@umdnj.edu
Siegel
David S
DS
Berenson
James
J
D019008:Drug Resistance, Neoplasm; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000503:physiopathology*; D016328:NF-kappa B / Q000096:biosynthesis / Q000502:physiology*; D011499:Protein Processing, Post-Translational
D016328:NF-kappa B