The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators.
The proto-oncoprotein Bcl-3 is a member of the IkappaB family and is present predominantly in the nucleus. To gain insight into specific nuclear functions of Bcl-3 we have isolated proteins that interact with its ankyrin repeat domain. Using the yeast two-hybrid-system we identified four novel binding partners of Bcl-3 in addition to NF-kappaB p50 and p52, previously known to associate with Bcl-3. The novel Bcl-3 interactors Jab1, Pirin, Tip60 and Bard1 are nuclear proteins which also bind to other transcription factors including c-Jun, nuclear factor I (NFI), HIV-1 Tat or the tumor suppressor and PolII holoenzyme component Brca1, respectively. Bcl-3, p50, and either Bard1, Tip60 or Pirin are sequestered into quarternary complexes on NF-kappaB DNA binding sites, whereas Jab1 enhances p50-Bcl-3-DNA complex formation. Furthermore, the histone acetylase Tip60 enhances Bcl-3-p50 activated transcription through an NF-kappaB binding site, indicating that quarternary complexes containing Bcl-3 interactors modulate NF-kappaB driven gene expression. These data implicate Bcl-3 as an adaptor between NF-kappaB p50/p52 and other transcription regulators and suggest that its gene activation function may at least in part be due to recruitment of the Tip60 histone actetylase.
Dechend
R
R
Max-Delbrück-Center for Molecular Medicine MDC, Berlin.
Hirano
F
F
Lehmann
K
K
Heissmeyer
V
V
Ansieau
S
S
Wulczyn
F G
FG
Scheidereit
C
C
Leutz
A
A
D000123:Acetyltransferases; D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D000081242:B-Cell Lymphoma 3 Protein; D001665:Binding Sites; D000075686:COP9 Signalosome Complex; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D049308:Dioxygenases; D006367:HeLa Cells / Q000378:metabolism; D051548:Histone Acetyltransferases; D006801:Humans; D020672:I-kappa B Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000074443:Lysine Acetyltransferase 5; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D015003:Yeasts / Q000235:genetics
D017487:Ankyrins; D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D049308:Dioxygenases; C105340:PIR protein, human; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex