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Publication : MEF2B Instructs Germinal Center Development and Acts as an Oncogene in B Cell Lymphomagenesis.

First Author  Brescia P Year  2018
Journal  Cancer Cell Volume  34
Issue  3 Pages  453-465.e9
PubMed ID  30205047 Mgi Jnum  J:265465
Mgi Id  MGI:6200933 Doi  10.1016/j.ccell.2018.08.006
Citation  Brescia P, et al. (2018) MEF2B Instructs Germinal Center Development and Acts as an Oncogene in B Cell Lymphomagenesis. Cancer Cell 34(3):453-465.e9
abstractText  The gene encoding the MEF2B transcription factor is mutated in germinal center (GC)-derived B cell lymphomas, but its role in GC development and lymphomagenesis is unknown. We demonstrate that Mef2b deletion reduces GC formation in mice and identify MEF2B transcriptional targets in GC, with roles in cell proliferation, apoptosis, GC confinement, and differentiation. The most common lymphoma-associated MEF2B mutant (MEF2B(D83V)) is hypomorphic, yet escapes binding and negative regulation by components of the HUCA complex and class IIa HDACs. Mef2b(D83V) expression in mice leads to GC enlargement and lymphoma development, a phenotype that becomes fully penetrant in combination with BCL2 de-regulation, an event associated with human MEF2B mutations. These results identify MEF2B as a critical GC regulator and a driver oncogene in lymphomagenesis.
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