A regulated nucleocytoplasmic shuttle contributes to Bright's function as a transcriptional activator of immunoglobulin genes

Molecular and Cellular Biology
Dongkyoon Kim, P W Tucker

Abstract

Bright/ARID3a has been implicated in mitogen- and growth factor-induced up-regulation of immunoglobulin heavy-chain (IgH) genes and in E2F1-dependent G1/S cell cycle progression. For IgH transactivation, Bright binds to nuclear matrix association regions upstream of certain variable region promoters and flanking the IgH intronic enhancer. While Bright protein was previously shown to reside within the nuclear matrix, we show here that a significant amount of Bright resides in the cytoplasm of normal and transformed B cells. Leptomycin B, chromosome region maintenance 1 (CRM1) overexpression, and heterokaryon experiments indicate that Bright actively shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner. We mapped the functional nuclear localization signal to the N-terminal region of REKLES, a domain conserved within ARID3 paralogues. Residues within the C terminus of REKLES contain its nuclear export signal, whose regulation is primarily responsible for Bright shuttling. Growth factor depletion and cell synchronization experiments indicated that Bright shuttling during S phase of the cell cycle leads to an increase in its nuclear abundance. Finally, we show that shuttle-incompetent Bright point mutants, even ...Continue Reading

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Citations

Feb 14, 2009·The EMBO Journal·Christian SchmidtPhilip W Tucker
Mar 11, 2015·The Journal of Experimental Medicine·Yan ZhouRichard R Hardy
Aug 19, 2016·PloS One·Jeffrey L KurkewichKaren D Cowden Dahl
Sep 5, 2015·European Journal of Immunology·Richard R Hardy, Kyoko Hayakawa
Apr 2, 2019·Frontiers in Immunology·Kyoko HayakawaRichard R Hardy
Apr 3, 2007·The Journal of Biological Chemistry·Dongkyoon KimPhilip W Tucker
Jan 1, 2017·Journal of Stem Cell Therapy and Transplantation·Melissa PopowskiHaley O Tucker

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