title: Targeting the GA binding protein beta1L isoform does not perturb lymphocyte development and function.
abstract: GA binding protein (GABP) is a ubiquitously expressed Ets family transcription factor that consists of two subunits, GABPalpha and GABPbeta. GABPalpha binds to DNA, and GABPbeta heterodimerizes with GABPalpha and possesses the ability to transactivate target genes. Our previous studies using GABPalpha-deficient mice revealed that GABPalpha is required for the development of both T and B cells. Two splice variants of GABPbeta are generated from the Gabpb1 locus and differ in their carboxy-terminal lengths and sequences. The longer isoform (GABPbeta1L) can homodimerize and thus form alpha(2)beta(2) tetramers depending on the gene context, whereas the shorter isoform (GABPbeta1S) cannot. In this study, we generated mice that are deficient in GABPbeta1L but that retain the expression of GABPbeta1S. Surprisingly, GABPbeta1L-/- mice had normal T- and B-cell development, and mature T and B cells showed normal responses to various stimuli. In contrast, targeting both GABPbeta1L and GABPbeta1S resulted in early embryonic lethality. Because of its incapability of forming homodimers, GABPbeta1S has been suspected to have a dominant negative role in regulating GABP target genes. Our findings argue against such a possibility and rather suggest that GABPbeta1S has a critical role in maintaining the transcriptional activity of the GABPalpha/beta complex.
authors.affiliation: Department of Microbiology, University of Iowa, 51 Newton Road, BSB 3-710, Iowa City, IA 52246, USA. hai-hui-xue@uiowa.edu
authors.forename: Hai-Hui
authors.initials: HH
authors.lastname: Xue
authors.forename: Xuefang
authors.initials: X
authors.lastname: Jing
authors.forename: Julie
authors.initials: J
authors.lastname: Bollenbacher-Reilley
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zhao
authors.forename: Jodie S
authors.initials: JS
authors.lastname: Haring
authors.forename: Baoli
authors.initials: B
authors.lastname: Yang
authors.forename: Chengyu
authors.initials: C
authors.lastname: Liu
authors.forename: Gail A
authors.initials: GA
authors.lastname: Bishop
authors.forename: John T
authors.initials: JT
authors.lastname: Harty
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D020964:Embryo Loss; D005091:Exons / Q000235:genetics; D051268:GA-Binding Protein Transcription Factor / Q000378:metabolism*; D018390:Gene Targeting; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D051268:GA-Binding Protein Transcription Factor; C495658:Gabpb1 protein, mouse; D020033:Protein Isoforms