{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Habib T"],"funding":["NIAID NIH HHS","NCI NIH HHS"],"pagination":["717-31"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2080907"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["179(4)"],"pubmed_abstract":["Deregulated expression of the Myc family of transcription factors (c-, N-, and L-myc) contributes to the development of many cancers by a mechanism believed to involve the stimulation of cell proliferation and inhibition of differentiation. However, using B cell-specific c-/N-myc double-knockout mice and E(mu)-myc transgenic mice bred onto genetic backgrounds (recombinase-activating gene 2-/- and Btk-/- Tec-/-) whereby B cell development is arrested, we show that Myc is necessary to stimulate both proliferation and differentiation in primary B cells. Moreover, Myc expression results in sustained increases in intracellular Ca2+ ([Ca2+]i), which is required for Myc to stimulate B cell proliferation and differentiation. The increase in [Ca2+]i correlates with constitutive nuclear factor of activated T cells (NFAT) nuclear translocation, reduced Ca2+ efflux, and decreased expression of the plasma membrane Ca2+-adenosine triphosphatase (PMCA) efflux pump. Our findings demonstrate a revised model whereby Myc promotes both proliferation and differentiation, in part by a remarkable mechanism whereby Myc amplifies Ca2+ signals, thereby enabling the concurrent expression of Myc- and Ca2+-regulated target genes."],"journal":["The Journal of cell biology"],"pubmed_title":["Myc stimulates B lymphocyte differentiation and amplifies calcium signaling."],"pmcid":["PMC2080907"],"funding_grant_id":["R01CA20525","R01AI0535468","R01 AI053568-05","R01 AI053568-03","R01 AI053568","R01 CA020525","R01 AI053568-04","R01 AI053568-01A1","R01 AI053568-02"],"pubmed_authors":["Park H","de Alboran IM","Eisenman RN","Rawlings DJ","Nicks A","Andrews S","Habib T","Tsang M","Wilson L","Iritani BM","Knoepfler PS"],"additional_accession":[]},"is_claimable":false,"name":"Myc stimulates B lymphocyte differentiation and amplifies calcium signaling.","description":"Deregulated expression of the Myc family of transcription factors (c-, N-, and L-myc) contributes to the development of many cancers by a mechanism believed to involve the stimulation of cell proliferation and inhibition of differentiation. However, using B cell-specific c-/N-myc double-knockout mice and E(mu)-myc transgenic mice bred onto genetic backgrounds (recombinase-activating gene 2-/- and Btk-/- Tec-/-) whereby B cell development is arrested, we show that Myc is necessary to stimulate both proliferation and differentiation in primary B cells. Moreover, Myc expression results in sustained increases in intracellular Ca2+ ([Ca2+]i), which is required for Myc to stimulate B cell proliferation and differentiation. The increase in [Ca2+]i correlates with constitutive nuclear factor of activated T cells (NFAT) nuclear translocation, reduced Ca2+ efflux, and decreased expression of the plasma membrane Ca2+-adenosine triphosphatase (PMCA) efflux pump. Our findings demonstrate a revised model whereby Myc promotes both proliferation and differentiation, in part by a remarkable mechanism whereby Myc amplifies Ca2+ signals, thereby enabling the concurrent expression of Myc- and Ca2+-regulated target genes.","dates":{"release":"2007-01-01T00:00:00Z","publication":"2007 Nov","modification":"2025-04-19T07:37:38.803Z","creation":"2019-03-26T23:02:29Z"},"accession":"S-EPMC2080907","cross_references":{"pubmed":["17998397"],"doi":["10.1083/jcb.200704173"]}}