| Authors | Sun, D., Stopka-Farooqui, U., Barry, S., Aksoy, E., Parsonage, G., Vossenkämper, A., Capasso, M., Wan, X., Norris, S., Marshall, J., Clear, A., Gribben, J., MacDonald, T., Buckley, C., Korbonits, M. and Haworth, O. |
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| Abstract | B cell lymphoma-6 (BCL6) is highly expressed in
germinal center B cells, but how its expression is
maintained is still not completely clear. Aryl hydrocarbon
receptor interacting protein (AIP) is a cochaperone
of heat shock protein 90. Deletion of
Aip in B cells decreased BCL6 expression, reducing
germinal center B cells and diminishing adaptive immune
responses. AIP was required for optimal AKT
signaling in response to B cell receptor stimulation,
and AIP protected BCL6 from ubiquitin-mediated
proteasomal degradation by the E3-ubiquitin ligase
FBXO11 by binding to the deubiquitinase UCHL1,
thus helping to maintain the expression of BCL6.
AIP was highly expressed in primary diffuse large
B cell lymphomas compared to healthy tissue and
other tumors. Our findings describe AIP as a positive
regulator of BCL6 expression with implications for
the pathobiology of diffuse large B cell lymphoma. |
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