PRDM1
PR domain zinc finger protein 1 also known as BLIMP-1 is a protein that in humans is encoded by the PRDM1 gene.[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]
Function
The increased expression of the Blimp-1 protein in B lymphocytes, T lymphocytes, NK cell and other key immune system effector cells leads to an immune response that is immediate and lasting, through proliferation and differentiation of antibody secreting plasma cells. In this setting among hematopoietic stem cells, Blimp-1 is considered a 'master regulator.'
The modular nature of Blimp-1 in the regulation of gene expression during B cell maturation was first reported by Dr. Mark Davis, et al. at Stanford:[3][4]
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.[5]
References
- ↑ Keller AD, Maniatis T (Jun 1991). "Identification and characterization of a novel repressor of beta-interferon gene expression". Genes Dev 5 (5): 868–79. doi:10.1101/gad.5.5.868. PMID 1851123.
- ↑ 2.0 2.1 "Entrez Gene: PRDM1 PR domain containing 1, with ZNF domain".
- ↑ Turner CA, Mack DH, Davis MM (April 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. PMID 8168136.
- ↑ Sciammas R, Davis MM (May 2004). "Modular nature of Blimp-1 in the regulation of gene expression during B cell maturation". J. Immunol. 172 (9): 5427–40. PMID 15100284.
- ↑ Best T, Li D, Skol AD, Kirchhoff T, Jackson SA, Yasui Y, Bhatia S, Strong LC, Domchek SM, Nathanson KL, Olopade OI, Huang RS, Mack TM, Conti DV, Offit K, Cozen W, Robison LL, Onel K (2011). "Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin's lymphoma". Nat. Med. 17 (8): 941–3. doi:10.1038/nm.2407. PMID 21785431. Lay summary – University of Chicago Medical Center.
Further reading
- Huang S (1994). "Blimp-1 is the murine homolog of the human transcriptional repressor PRDI-BF1.". Cell 78 (1): 9. doi:10.1016/0092-8674(94)90565-7. PMID 8033216.
- Mock BA, Liu L, LePaslier D, Huang S (1997). "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. PMID 8921366.
- Ren B, Chee KJ, Kim TH, Maniatis T (1999). "PRDI-BF1/Blimp-1 repression is mediated by corepressors of the Groucho family of proteins". Genes Dev. 13 (1): 125–37. doi:10.1101/gad.13.1.125. PMC 316372. PMID 9887105.
- Angelin-Duclos C, Cattoretti G, Lin KI, Calame K (2000). "Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo". J. Immunol. 165 (10): 5462–71. PMID 11067898.
- Gupta S, Anthony A, Pernis AB (2001). "Stage-specific modulation of IFN-regulatory factor 4 function by Krüppel-type zinc finger proteins". J. Immunol. 166 (10): 6104–11. PMID 11342629.
- Medina F, Segundo C, Campos-Caro A, et al. (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. PMID 11877292.
- Shaffer AL, Lin KI, Kuo TC, et al. (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. PMID 12150891.
- Vasanwala FH, Kusam S, Toney LM, Dent AL (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". J. Immunol. 169 (4): 1922–9. PMID 12165517.
- Borson ND, Lacy MQ, Wettstein PJ (2003). "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. PMID 12453881.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Györy I, Fejér G, Ghosh N, et al. (2003). "Identification of a functionally impaired positive regulatory domain I binding factor 1 transcription repressor in myeloma cell lines". J. Immunol. 170 (6): 3125–33. PMID 12626569.
- Gyory I, Wu J, Fejér G, et al. (2004). "PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing". Nat. Immunol. 5 (3): 299–308. doi:10.1038/ni1046. PMID 14985713.
- Lotz C, Mutallib SA, Oehlrich N, et al. (2005). "Targeting positive regulatory domain I-binding factor 1 and X box-binding protein 1 transcription factors by multiple myeloma-reactive CTL". J. Immunol. 175 (2): 1301–9. PMID 16002735.
- Tam W, Gomez M, Chadburn A, et al. (2006). "Mutational analysis of PRDM1 indicates a tumor-suppressor role in diffuse large B-cell lymphomas". Blood 107 (10): 4090–100. doi:10.1182/blood-2005-09-3778. PMID 16424392.
- Pasqualucci L, Compagno M, Houldsworth J, et al. (2006). "Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma". J. Exp. Med. 203 (2): 311–7. doi:10.1084/jem.20052204. PMC 2118216. PMID 16492805.
- González-García I, Ocaña E, Jiménez-Gómez G, et al. (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". J. Immunol. 176 (7): 4042–50. PMID 16547239.
- Garcia JF, Roncador G, García JF, et al. (2006). "PRDM1/BLIMP-1 expression in multiple B and T-cell lymphoma". Haematologica 91 (4): 467–74. PMID 16585013.
- Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
External links
- PRDM1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
- FactorBook PRDM1
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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