TY - JOUR
T1 - Aryl hydrocarbon receptor interacting protein maintains germinal center B cells through suppression of BCL6 degradation
AU - Sun, Dijue
AU - Stopka-Farooqui, Urszula
AU - Barry, Sayka
AU - Askoy, Ezra
AU - Parsonage, Gregory
AU - Vossenkamper, Anna
AU - Capasso, Melanie
AU - Wan, Xinyu
AU - Norris, Sherine
AU - Marshall, Jennifer
AU - Clear, Andrew
AU - Gribben, John
AU - MacDonald, Thomas T.
AU - Buckley, Christopher
AU - Korbonits, Marta
AU - Haworth, Oliver
PY - 2019/4/30
Y1 - 2019/4/30
N2 - 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 co-chaperone 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. BCL6 overexpression contributes to the pathobiology of diffuse large B cell lymphoma (DLBCL). Sun et al. find that the co-chaperone aryl hydrocarbon receptor interacting protein (AIP), whose high expression is associated with reduced survival of DLBCL patients, helps maintain BCL6 expression by facilitating the removal of ubiquitin from BCL6.
AB - 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 co-chaperone 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. BCL6 overexpression contributes to the pathobiology of diffuse large B cell lymphoma (DLBCL). Sun et al. find that the co-chaperone aryl hydrocarbon receptor interacting protein (AIP), whose high expression is associated with reduced survival of DLBCL patients, helps maintain BCL6 expression by facilitating the removal of ubiquitin from BCL6.
KW - AIP
KW - BCL6
KW - FBXO11
KW - UCHL1
KW - lymphoma
KW - ubiquitination
UR - http://www.scopus.com/inward/record.url?scp=85064552972&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2019.04.014
DO - 10.1016/j.celrep.2019.04.014
M3 - Article
SN - 2211-1247
VL - 27
SP - 1464
EP - 1471
JO - Cell Reports
JF - Cell Reports
IS - 5
M1 - e4
ER -