ABSTRACT
The NF-κB family of transcription factors is composed of homo-and heterodimers of REL homology domain (RHD)-containing polypeptides. The RHD is a 300-amino-acid domain that mediates protein-protein interactions as well as DNA binding. Mammals contain •ve RHDcontaining proteins NF-κB1, NF-κB2, REL, RELA, and RELB. The RHDs of REL family members are located at the N-termini of these proteins. NF-κB1 and NF-κB2, the longest polypeptides (105 and 100 kD, respectively), are further processed to generate p50 and p52 proteins that are composed mostly of the RHD itself (Basak et al. 2007). p50 forms homodimers and heterodimerizes primarily with RELA (p65) and REL; p52 also forms homodimers but heterodimerizes primarily with RELB. Thus, despite substantial homology between these proteins, p50 and p52 serve different cellular functions. The other three REL family members (REL, RELA, and RELB) contain C-terminal extensions beyond the RHD that act as transcription activation domains. REL and RELA can form homodimers and REL/RELA heterodimers in addition to p50-containing heterodimers. RELB is believed not to homodimerize and forms heterodimers largely with p52 (Bonizzi and Karin 2004). REL, RELA, and RELB polypeptides do not undergo proteolytic processing but can be posttranslationally modi•ed by phosphorylation and acetylation (Chen and Greene 2003; Neumann and Naumann 2007). These modi•cations have been shown to alter their transcriptional properties. It is obvious that “NF-κB” constitutes a family of DNA binding proteins, thus analysis of NF-κB-dependent gene transcription must account for which family member(s) is being used to activate genes of interest.
