The proto-oncogene BCL6 encodes for a BTB/POZ-zinc finger transcriptional repressor which plays an essential role in germinal center (GC) formation and is implicated in the pathogenesis of B-cell lymphoma. BCL6 is shown to be a critical regulator modulating many important functions in B cells, including activation, differentiation, cell cycle arrest and apoptosis. Tight regulation of BCL6 is, therefore, critical for the control of GC reaction as well as for the phenotype of GC-derived lymphomas. In response to B cell receptor activation or DNA damage induction, BCL6 protein is phosphorylated and subsequently degraded through distinct mechanisms that involve ubiquitination process. Here we report that BCL6 interacts with Cullin-3 (Cul3), major component of a multimeric E3 ubiquitin ligase complex. Consistent with previous reports indicating that BTB/POZ domain proteins interact with Cul3, the BCL6-POZ domain is sufficient for BCL6 interaction with Cul3. Importantly, BCL6 and Cul3 interaction is also readily detected in native B cells. Interestingly, this interaction does not affect BCL6 transcriptional repression activity nor does it affect basal level of BCL6 stability. The pathophysiological consequence of this interaction is investigated, including a possibility that BCL6 functions as a specific substrate adaptor for the Cullin-3 ubiquitin complex.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.