The Epigenetics of Autoimmune Diseases (Zouali/The Epigenetics of Autoimmune Diseases) || The Role of NF-κB in Central Tolerance

✍ Scribed by Zouali, Moncef

• Publisher: John Wiley & Sons, Ltd
• Year: 2009
• Tongue: English
• Weight: 255 KB
• Edition: 1
• Category: Article
• ISBN: 0470758619
• DOI: 10.1002/9780470743553.ch3

✦ Synopsis

Nuclear factor kB (NF-kB) is a family of structurally related transcription factors. In mammals, the NF-kB family consists of five members: NF-kB1 (p105/50), NF-kB2 (p100/52), RelA (p65), RelB and c-Rel. They all have a structurally conserved N-terminal 300-amino-acid Rel homology domain (RHD), which contains sequences responsible for dimerization, nuclear translocation and DNA binding. Only RelA, RelB and c-Rel have a transactivation domain, which is non-homologous and located at the C-termini of the proteins. The other two NF-kB proteins, NF-kB1 and NF-kB2, lack a transactivation domain but instead contain seven ankyrin repeats, a 33-amino-acid characteristic motif of inhibitor of NF-kB (IkB) that mediates protein-protein interactions. Although RelA, RelB and c-Rel are expressed as their mature forms, NF-kB1 and NF-kB2 are generated as precursor proteins, p105 and p100 respectively. The ankyrin repeats containing NF-kB1 (p105) and NF-kB2 (p100) can function as IkB-like proteins to retain NF-kB in the cytoplasm. The ankyrin domain is proteolytically cleaved and degraded for generation of the mature forms of NF-kB1 (p50) and NF-kB 2 (p52). The five NF-kB proteins can form 15 transcription factors through homo-or heterodimerization . However, not all of them have transactivation activity. Homodimers of p50 and p52 can bind to DNA, but function as transcription repressors since they lack a transactivation domain. However, they can stimulate transcription when binding to Bcl-3, an IkB-like protein. The main activated forms of NF-kB include RelA:p50 and RelB:p52. NF-kB family members play critical roles in a