TAILIEUCHUNG - Báo cáo khoa học: PRDM1/Blimp1 downregulates expression of germinal center genes LMO2 and HGAL

Human germinal center-associated lymphoma (HGAL) and LIM domain only-2 (LMO2) are proteins highly expressed in germinal center (GC) B lymphocytes. HGAL and LMO2 are also expressed in GC-derived lymphomas and distinguish biologically distinct subgroups of diffuse large B-cell lymphomas (DLBCL) associated with improved survival. | IFEBS Journal PRDM1 Blimp1 downregulates expression of germinal center genes LMO2 and HGAL Elena Cubedo1 Michelle Maurin2 Xiaoyu Jiang1 Izidore S. Lossos1 f and Kenneth L. Wright2 f 1 Department of Medicine and Molecular and Cellular Pharmacology Sylvester Comprehensive Cancer Center University of Miami FL USA 2 Immunology Program H. Lee Moffitt Cancer Center and Research Institute Tampa FL USA Keywords Blimp-1 HGAL LMO2 non-Hodgkin s B-cell lymphoma transcription Correspondence K. L. Wright H. Lee Moffitt Cancer Center MRC4E 12902 Magnolia Drive Tampa FL 33612 USA Fax 1 813 745 7264 Tel 1 813 745 3918 E-mail Note t these sets of authors contributed equally to this work Received 26 April 2011 revised 23 May 2011 accepted 28 June 2011 doi Human germinal center-associated lymphoma HGAL and LIM domain only-2 LMO2 are proteins highly expressed in germinal center GC B lymphocytes. HGAL and LMO2 are also expressed in GC-derived lymphomas and distinguish biologically distinct subgroups of diffuse large B-cell lymphomas DLBCL associated with improved survival. However little is known about their regulation. PRDM1 Blimp1 is a master regulator of terminal B cell differentiation and may also function as a tumor suppressor in the pathogenesis of DLBCL where it is frequently inactivated by mutations and deletions. We now demonstrate that both HGAL and LMO2 are directly regulated by the transcription repressor PRDM1. In vivo studies demonstrate that PRDM1 directly binds to the recognition sites within the upstream promoters of both HGAL and LMO2. PRDM1 binding suppresses endogenous protein and mRNA levels of HGAL and LMO2. In addition promoter analysis reveals that site-specific binding of PRDM1 to the promoters is capable of repressing transcriptional activity. This inhibitory effect of PRDM1 suggests that it has a key role in the loss of HGAL and LMO2 expression upon differentiation of GC B cells to plasma cells and may .

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