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Regulation of BOB.1/OBF.1 stability by SIAH
Author(s) -
Boehm Jannic,
He Yunsheng,
Greiner Axel,
Staudt Louis,
Wirth Thomas
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.15.4153
Subject(s) - biology , coactivator , germinal center , downregulation and upregulation , microbiology and biotechnology , proteasome , messenger rna , b cell , transcription factor , genetics , gene , antibody
The BOB.1/OBF.1 coactivator is critically involved in mediating octamer‐dependent transcriptional activity in B lymphocytes. Mice lacking this coactivator show various defects in B‐cell development, most notably they completely lack germinal centers. Consistent with this phenotype, BOB.1/OBF.1 levels are massively upregulated in germinal center B cells as compared with resting B cells. We have addressed the mechanism of upregulation and found that only a minor part of this regulation can be attributed to increased levels of BOB.1/OBF.1‐specific mRNA. Apparently, BOB.1/OBF.1 is also regulated at the protein level. In support of this suggestion we have been able to identify two related BOB.1/OBF.1 interacting proteins, SIAH1 and SIAH2, in a yeast two‐hybrid screen. SIAH1 and SIAH2 are known regulators of protein stability. Cotransfection experiments revealed that coexpression of SIAH results in a destabilization of BOB.1/OBF.1 protein without affecting mRNA levels. Further more, proteasome inhibitors block the degradation of BOB.1/OBF.1 protein. Finally, B‐cell receptor cross‐linking also resulted in the degradation of BOB.1/OBF.1 and consequently reduced transcriptional activation of BOB.1/OBF.1‐dependent reporters.