Aryl hydrocarbon receptor interacting protein (AIP) protection of Bcl-6

Aryl hydrocarbon receptor interacting protein (AIP) is a co-chaperone molecule that can bind to many proteins including heat shock protein-90 (Hsp90). We found that AIP conditionally deleted in B cells resulted in decreased germinal centre (GC) B cells and decreased expression of the proto-oncogene B cell lymphoma-6 (Bcl-6) that is over-expressed in many aggressive B cell lymphomas that are difficult to treat with conventional drugs. We found that AIP could bind to Bcl-6 and treatment of AIP-deficient B cells with a proteasome inhibitor increased Bcl-6 expression indicating that AIP protects Bcl-6 from being degraded, but it is not known how this occurs. AIP might function as a tumour promoter by protecting Bcl-6 from degradation.

We will study the molecular mechanisms by which AIP regulates Bcl-6 and test the effectiveness of inhibiting AIP on tumour growth in vivo. 

AIP would be a therapeutically attractive target, as it would lead to the loss of Bcl-6 and the treatment of aggressive B cell lymphomas.