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BCL-3 degradation involves its polyubiquitination through a FBW7-independent pathway and its binding to the proteasome subunit PSMB1

par Keutgens, Aurore;Zhang, Xin;Shostak, Kateryna;Robert, Isabelle;Olivier, Sabine;Vanderplasschen, Alain;Chapelle, Jean-Paul;Viatour, Patrick;Merville, Marie-Paule;Bex, Françoise ;Gothot, André;Chariot, Alain
Référence The Journal of biological chemistry, 285, 33, page (25831-25840)
Publication Publié, 2010-08

Article révisé par les pairs

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Résumé :

The oncogenic protein BCL-3 activates or represses gene transcription through binding with the NF-κB 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 Lys48-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 a 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 IκB protein. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.