BCL6 Interacts with Cullin-3 Ubiquitin Ligase Complex In B Cells
Abstract 3129 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...
Saved in:
| Published in: | Blood Vol. 116; no. 21; p. 3129 |
|---|---|
| Main Authors: | , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Elsevier Inc
19-11-2010
|
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Abstract 3129
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. |
|---|---|
| ISSN: | 0006-4971 1528-0020 |
| DOI: | 10.1182/blood.V116.21.3129.3129 |