PR domain zinc finger protein 1 also known as BLIMP-1 is a protein that in humans is encoded by the PRDM1gene.[1][2] BLIMP-1 acts as a repressor of beta-interferon (β-IFN) gene expression. The protein binds specifically to the PRDI (positive regulatory domain I element) of the β-IFN gene promoter. Transcription of this gene increases upon virus induction.[2]
The increased expression of the Blimp-1 protein in B lymphocytes, T lymphocytes, NK cell and other immune system cells leads to an immune response through proliferation and differentiation of antibody secreting plasma cells. Blimp-1 is also considered a 'master regulator' of hematopoietic stem cells.[3][4]
Blimp1 (also known as Prdm1), a known transcriptional repressor, has a critical role in the foundation of the mouse germ cell lineage, as its disruption causes a block early in the process of primordial germ cell formation. Blimp1-deficient mutant embryos form a tight cluster of about 20 primordial germ cell-like cells, which fail to show the characteristic migration, proliferation and consistent repression of homeobox genes that normally accompany specification of primordial germ cells. The genetic lineage-tracing experiments indicate that the Blimp1-positive cells originating from the proximal posterior epiblast cells are indeed the lineage-restricted primordial germ cell precursors.[5]
Second cancers after radiation treatment
A genome-wide association study has identified two genetic variations near the PRDM1 gene that predict an increased likelihood of developing a second cancer after radiation treatment for Hodgkin lymphoma.[6]
References
↑Keller AD, Maniatis T (May 1991). "Identification and characterization of a novel repressor of beta-interferon gene expression". Genes & Development. 5 (5): 868–79. doi:10.1101/gad.5.5.868. PMID1851123.
↑Turner CA, Mack DH, Davis MM (Apr 1994). "Blimp-1, a novel zinc finger-containing protein that can drive the maturation of B lymphocytes into immunoglobulin-secreting cells". Cell. 77 (2): 297–306. doi:10.1016/0092-8674(94)90321-2. PMID8168136.
↑Sciammas R, Davis MM (May 2004). "Modular nature of Blimp-1 in the regulation of gene expression during B cell maturation". Journal of Immunology. 172 (9): 5427–40. doi:10.4049/jimmunol.172.9.5427. PMID15100284.
↑Ohinata Y, Payer B, O'Carroll D, Ancelin K, Ono Y, Sano M, Barton SC, Obukhanych T, Nussenzweig M, Tarakhovsky A, Saitou M, Surani MA (Jul 2005). "Blimp1 is a critical determinant of the germ cell lineage in mice". Nature. 436 (7048). doi:10.1038/nature03813. PMID15937476.
Mock BA, Liu L, LePaslier D, Huang S (Oct 1996). "The B-lymphocyte maturation promoting transcription factor BLIMP1/PRDI-BF1 maps to D6S447 on human chromosome 6q21-q22.1 and the syntenic region of mouse chromosome 10". Genomics. 37 (1): 24–8. doi:10.1006/geno.1996.0516. PMID8921366.
Angelin-Duclos C, Cattoretti G, Lin KI, Calame K (Nov 2000). "Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo". Journal of Immunology. 165 (10): 5462–71. doi:10.4049/jimmunol.165.10.5462. PMID11067898.
Gupta S, Anthony A, Pernis AB (May 2001). "Stage-specific modulation of IFN-regulatory factor 4 function by Krüppel-type zinc finger proteins". Journal of Immunology. 166 (10): 6104–11. doi:10.4049/jimmunol.166.10.6104. PMID11342629.
Medina F, Segundo C, Campos-Caro A, González-García I, Brieva JA (Mar 2002). "The heterogeneity shown by human plasma cells from tonsil, blood, and bone marrow reveals graded stages of increasing maturity, but local profiles of adhesion molecule expression". Blood. 99 (6): 2154–61. doi:10.1182/blood.V99.6.2154. PMID11877292.
Shaffer AL, Lin KI, Kuo TC, Yu X, Hurt EM, Rosenwald A, Giltnane JM, Yang L, Zhao H, Calame K, Staudt LM (Jul 2002). "Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program". Immunity. 17 (1): 51–62. doi:10.1016/S1074-7613(02)00335-7. PMID12150891.
Vasanwala FH, Kusam S, Toney LM, Dent AL (Aug 2002). "Repression of AP-1 function: a mechanism for the regulation of Blimp-1 expression and B lymphocyte differentiation by the B cell lymphoma-6 protooncogene". Journal of Immunology. 169 (4): 1922–9. doi:10.4049/jimmunol.169.4.1922. PMID12165517.
Borson ND, Lacy MQ, Wettstein PJ (Dec 2002). "Altered mRNA expression of Pax5 and Blimp-1 in B cells in multiple myeloma". Blood. 100 (13): 4629–39. doi:10.1182/blood.V100.13.4629. PMID12453881.
Györy I, Fejér G, Ghosh N, Seto E, Wright KL (Mar 2003). "Identification of a functionally impaired positive regulatory domain I binding factor 1 transcription repressor in myeloma cell lines". Journal of Immunology. 170 (6): 3125–33. doi:10.4049/jimmunol.170.6.3125. PMID12626569.
Gyory I, Wu J, Fejér G, Seto E, Wright KL (Mar 2004). "PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing". Nature Immunology. 5 (3): 299–308. doi:10.1038/ni1046. PMID14985713.
Lotz C, Mutallib SA, Oehlrich N, Liewer U, Ferreira EA, Moos M, Hundemer M, Schneider S, Strand S, Huber C, Goldschmidt H, Theobald M (Jul 2005). "Targeting positive regulatory domain I-binding factor 1 and X box-binding protein 1 transcription factors by multiple myeloma-reactive CTL". Journal of Immunology. 175 (2): 1301–9. doi:10.4049/jimmunol.175.2.1301. PMID16002735.
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González-García I, Ocaña E, Jiménez-Gómez G, Campos-Caro A, Brieva JA (Apr 2006). "Immunization-induced perturbation of human blood plasma cell pool: progressive maturation, IL-6 responsiveness, and high PRDI-BF1/BLIMP1 expression are critical distinctions between antigen-specific and nonspecific plasma cells". Journal of Immunology. 176 (7): 4042–50. doi:10.4049/jimmunol.176.7.4042. PMID16547239.
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