Stabilization of RelB requires multidomain interactions with p100/p52.
The NF-kappaB family member RelB has many properties not shared by other family members such as restricted subunit association and lack of regulation by the classical IkappaB proteins. We show that the protein level of RelB is significantly reduced in the absence of p100 and reduced even more when both p100 and p105 are absent. RelB stabilizes itself by directly interacting with p100, p105, and their processed products. However, RelB forms complexes with its partners using different interaction modes. Although the C-terminal ankyrin repeat domain of p105 is not involved in the RelB-p105 complex formation, all domains and flexible regions of each protein are engaged in the RelB-p100 complex. In several respects the RelB-p52 and RelB-p100 complexes are unique in the NF-kappaB family. The N-terminal domain of p100/p52 interacts with RelB but not RelA. The transcriptional activation domain of RelB, but not RelA, directly interacts with the processing region of p100. These unique protein-protein contacts explain why RelB prefers p52 as its dimeric partner for transcriptional activity and is retained in the cytoplasm as an inhibited complex by p100. This association-mediated stabilization of RelB implies a possible role for RelB in the processing of p100 into p52.
Fusco
Amanda J
AJ
Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Savinova
Olga V
OV
Talwar
Rashmi
R
Kearns
Jeffrey D
JD
Hoffmann
Alexander
A
Ghosh
Gourisankar
G
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D019281:Dimerization; D006801:Humans; D051379:Mice; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D052003:NF-kappa B p52 Subunit / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D051841:Transcription Factor RelB / Q000737:chemistry* / Q000378:metabolism*
D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D051841:Transcription Factor RelB