Nuclear factor-kappaB1: regulation and function.
The transcription factor NF-kappaB is a critical regulator of many cellular processes including cell survival and inflammation. NF-kappaB functions as a hetero- or homo-dimer which can be formed from five NF-kappaB subunits, NF-kappaB1 (p50 and its precursor p105), NF-kappaB2 (p52 and its precursor p100), RelA (p65), RelB and c-Rel. The most studied dimer is p50:p65, which is activated by the classical pathway and usually promotes gene expression. Activation of p50:p65 is linked with cell survival and promoting inflammation. This review provides a detailed overview of the structure, synthesis and function of the lesser characterised NF-kappaB subunit; NF-kappaB1 (p105 and p50). The diverse interactions of NF-kappaB1 with co-activators, co-repressors and other signaling networks that influence NF-kappaB1 gene expression are discussed. Finally the anti-inflammatory actions of NF-kappaB1 signaling will be assessed and the crucial need to design novel therapeutic drugs which exploit and amplify the anti-inflammatory actions of p50 will be explored.
Pereira
Silvia Gaspar
SG
Liver Research Group, Institute of cellular Medicine, 4th Floor catherine Cookson Building, Framlington Place, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK.
Oakley
Fiona
F
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019281:Dimerization; D006801:Humans; D052002:NF-kappa B p50 Subunit / Q000502:physiology*; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D052002:NF-kappa B p50 Subunit