A signaling pathway mediating downregulation of BCL6 in germinal center B cells is blocked by BCL6 gene alterations in B cell lymphoma - PubMed (original) (raw)
A signaling pathway mediating downregulation of BCL6 in germinal center B cells is blocked by BCL6 gene alterations in B cell lymphoma
Masumichi Saito et al. Cancer Cell. 2007 Sep.
Free article
Erratum in
- Cancer Cell. 2007 Oct;12(4):403
Abstract
The BCL6 proto-oncogene encodes a transcriptional repressor necessary for the development of germinal centers (GCs) and directly implicated in lymphomagenesis. Post-GC development of B cells requires BCL6 downregulation, while its constitutive expression caused by chromosomal translocations leads to diffuse large B cell lymphoma (DLBCL). Herein we identify a signaling pathway that downregulates BCL6 expression in normal GC B cells and is blocked in a subset of DLBCL due to alterations in the BCL6 gene. Activation of the CD40 receptor leads to NF-kappaB-mediated induction of the IRF4 transcription factor, which, in turn, represses BCL6 expression by binding to its promoter region. A subset of DLBCL displays chromosomal translocations or mutations that disrupt the IRF4-responsive region in the BCL6 promoter and block its downregulation by CD40 signaling.
Comment in
- The endless complexity of lymphocyte differentiation and lymphomagenesis: IRF-4 downregulates BCL6 expression.
Lossos IS. Lossos IS. Cancer Cell. 2007 Sep;12(3):189-91. doi: 10.1016/j.ccr.2007.08.012. Cancer Cell. 2007. PMID: 17785200
Similar articles
- The endless complexity of lymphocyte differentiation and lymphomagenesis: IRF-4 downregulates BCL6 expression.
Lossos IS. Lossos IS. Cancer Cell. 2007 Sep;12(3):189-91. doi: 10.1016/j.ccr.2007.08.012. Cancer Cell. 2007. PMID: 17785200 - The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells.
Phan RT, Dalla-Favera R. Phan RT, et al. Nature. 2004 Dec 2;432(7017):635-9. doi: 10.1038/nature03147. Nature. 2004. PMID: 15577913 - p110δ phosphoinositide 3-kinase represses IgE switch by potentiating BCL6 expression.
Zhang TT, Makondo KJ, Marshall AJ. Zhang TT, et al. J Immunol. 2012 Apr 15;188(8):3700-8. doi: 10.4049/jimmunol.1103302. Epub 2012 Mar 14. J Immunol. 2012. PMID: 22422878 - The BCL6 proto-oncogene: a leading role during germinal center development and lymphomagenesis.
Jardin F, Ruminy P, Bastard C, Tilly H. Jardin F, et al. Pathol Biol (Paris). 2007 Feb;55(1):73-83. doi: 10.1016/j.patbio.2006.04.001. Epub 2006 Jul 3. Pathol Biol (Paris). 2007. PMID: 16815642 Review. - BCL6: master regulator of the germinal center reaction and key oncogene in B cell lymphomagenesis.
Basso K, Dalla-Favera R. Basso K, et al. Adv Immunol. 2010;105:193-210. doi: 10.1016/S0065-2776(10)05007-8. Adv Immunol. 2010. PMID: 20510734 Review.
Cited by
- Advances in biology, diagnosis and treatment of DLBCL.
Shi Y, Xu Y, Shen H, Jin J, Tong H, Xie W. Shi Y, et al. Ann Hematol. 2024 Sep;103(9):3315-3334. doi: 10.1007/s00277-024-05880-z. Epub 2024 Jul 17. Ann Hematol. 2024. PMID: 39017945 Free PMC article. Review. - The F-box E3 ligase protein FBXO11 regulates EBNA3C-associated degradation of BCL6.
Sun K, Bose D, Singh RK, Pei Y, Robertson ES. Sun K, et al. J Virol. 2024 Jul 23;98(7):e0054824. doi: 10.1128/jvi.00548-24. Epub 2024 Jun 12. J Virol. 2024. PMID: 38864622 Free PMC article. - Stochastic modeling of a gene regulatory network driving B cell development in germinal centers.
Koshkin A, Herbach U, Martínez MR, Gandrillon O, Crauste F. Koshkin A, et al. PLoS One. 2024 Mar 28;19(3):e0301022. doi: 10.1371/journal.pone.0301022. eCollection 2024. PLoS One. 2024. PMID: 38547073 Free PMC article. - Interleukin-4 downregulates transcription factor BCL6 to promote memory B cell selection in germinal centers.
Shehata L, Thouvenel CD, Hondowicz BD, Pew LA, Pritchard GH, Rawlings DJ, Choi J, Pepper M. Shehata L, et al. Immunity. 2024 Apr 9;57(4):843-858.e5. doi: 10.1016/j.immuni.2024.02.018. Epub 2024 Mar 20. Immunity. 2024. PMID: 38513666 - Delineating the mechanism of fragility at BCL6 breakpoint region associated with translocations in diffuse large B cell lymphoma.
Gopalakrishnan V, Roy U, Srivastava S, Kariya KM, Sharma S, Javedakar SM, Choudhary B, Raghavan SC. Gopalakrishnan V, et al. Cell Mol Life Sci. 2024 Jan 10;81(1):21. doi: 10.1007/s00018-023-05042-w. Cell Mol Life Sci. 2024. PMID: 38196006 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous