American Society for Biochemistry and Molecular Biology
Yes (verified by ORBi)
BCL-3 ; polyubiquitination
[en] NF kappa B ; proteasome
[en] The oncogenic protein BCL-3 activates or represses gene transcription through binding with the NF-kappaB proteins p50 and p52 and is degraded through a phospho- and GSK3-dependent pathway. However, the mechanisms underlying its degradation remain poorly understood. Yeast-two-hybrid analysis led to the identification of the proteasome subunit PSMB1 as a BCL-3-associated protein. The binding of BCL-3 to PSMB1 is required for its degradation through the proteasome. Indeed, PSMB1-depleted cells are defective in degrading polyubiquitinated BCL-3. The N-terminal part of BCL-3 includes lysines 13 and 26 required for the K48-linked polyubiquitination of BCL-3. Moreover, the E3 ligase FBW7 known to polyubiquitinate a variety of substrates phosphorylated by GSK3 is dispensable for BCL-3 degradation. Thus, our data defined an unique motif of BCL-3 that is needed for its recruitment to the proteasome and identified PSMB1 as a key protein required for the proteasome-mediated degradation of a nuclear and oncogenic IkappaB protein.
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS, TELEVIE, FBC