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* H. Lee Moffitt Cancer Center and Research Institute, Department of Interdisciplinary Oncology and
Department of Biochemistry and Molecular Biology, University of South Florida, Tampa, FL 33612
B cell differentiation into a plasma cell requires expression of the positive regulatory domain zinc finger protein 1 gene (PRDM1) that encodes the positive regulatory domain I binding factor 1 (PRDI-BF1 or Blimp-1) protein. It represses the transcription of specific target genes, including c-myc, the MHC class II trans-activator, Pax-5, and CD23b. In this study we demonstrate the presence of an alternative protein product of the PRDM1 gene. The new protein, PRDI-BF1
, has a disrupted PR domain and lacks the amino-terminal 101 aa of the originally described protein. PRDI-BF1 has a dramatic loss of repressive function on multiple target genes, but maintains normal DNA-binding activity, nuclear localization, and association with histone deacetylases and deacetylase activity. Myeloma cell lines express the highest levels of PRDM1 mRNA relative to the full-length form, while primary cells and several other cell lines have very low, but detectable, levels of PRDM1. RNA analysis and analysis of the PRDM1 promoters demonstrate that PRDI-BF1 is generated from the same gene by alternative transcription initiation using an internal promoter. These newly described features of the PRDM1 gene are highly analogous to the PRDM2 (RIZ) and PRDM3 (MDS1-EVI1) genes, in which each express a truncated protein missing the PR domain. The expression of each of the truncated proteins is elevated in cancerous cells and may play an important role in the disease.
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