title: Activation of Aicda gene transcription by Pax5 in plasmacytoma cells.
abstract: Activation-induced deaminase (AID) is an enzyme responsible for somatic hypermutation and immunoglobulin heavy chain class switch recombination. Because AID causes double-stranded breaks in DNA, its expression is highly regulated and is normally restricted to germinal-center B cells. Dysregulated AID expression can lead to cancer as a result of AID-mediated chromosomal translocations. Many transcription factors including paired box protein 5 (Pax5) have been implicated in regulating the expression of Aicda, the gene encoding AID. In this study, we demonstrate that exogenous expression of Pax5 in a murine plasmacytoma cell line, 558LμM, leads to robust activation of endogenous Aicda transcription. Pax5 is known to initiate transcription through both its N-terminal-paired DNA-binding domain and its C-terminal-activation domain. Through mutational analysis, we demonstrate that Pax5 regulates Aicda transcription through its C-terminal-activation domain. Together, our work describes a novel system that will be useful for determining how Pax5 regulates Aicda transcription.
authors.affiliation: Integrated Department of Immunology, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Carissa
authors.initials: C
authors.lastname: Dege
authors.forename: James
authors.initials: J
authors.lastname: Hagman
mesh_terms: D000818:Animals; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics*; D051379:Mice; D051757:PAX5 Transcription Factor / Q000235:genetics*; D010954:Plasmacytoma; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D051757:PAX5 Transcription Factor; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase