title: Charged Amino Acid-rich Leucine Zipper-1 (Crlz-1) as a Target of Wnt Signaling Pathway Controls Pre-B Cell Proliferation by Affecting Runx/CBFβ-targeted VpreB and λ5 Genes.
abstract: The proliferation of pre-B cells is known to further increase the clonal diversity of B cells at the stage of pre-B cells by allowing the same rearranged heavy chains to combine with differently rearranged light chains in a subsequent developmental stage. Crlz-1 (charged amino acid-rich leucine zipper-1) was found to control this proliferation of pre-B cells by working as a Wnt (wingless-related mouse mammary tumor virus integration site) target gene in these cells. Mechanistically, Crlz-1 protein functioned by mobilizing cytoplasmic CBFβ (core binding factor β) into the nucleus to allow Runx (runt-related transcription factor)/CBFβ heterodimerization. Runx/CBFβ then turned on its target genes such as EBF (early B cell factor), VpreB, and λ5 and thereby pre-B cell receptor signaling, leading to the expression of cyclins D2 and D3 Actually, the proliferative function of Crlz-1 was demonstrated by not only Crlz-1 or β-catenin knockdown but also Crlz-1 overexpression. Furthermore, the mechanistic view that the proliferative function of Crlz-1 is caused by relaying Wnt/β-catenin to pre-B cell receptor signaling pathways through the regulation of Runx/CBFβ heterodimerization was also verified by employing niclosamide, XAV939, and LiCl as Wnt inhibitors and activator, respectively.
authors.affiliation: From the Department of Genetic Engineering, College of Life Sciences, Kyung Hee University, Gyeonggi-do 17104, Republic of Korea.
authors.forename: Seung-Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: From the Department of Genetic Engineering, College of Life Sciences, Kyung Hee University, Gyeonggi-do 17104, Republic of Korea.
authors.forename: Sung-Kyun
authors.initials: SK
authors.lastname: Park
authors.affiliation: From the Department of Genetic Engineering, College of Life Sciences, Kyung Hee University, Gyeonggi-do 17104, Republic of Korea.
authors.forename: Han-Woong
authors.initials: HW
authors.lastname: Yoo
authors.affiliation: From the Department of Genetic Engineering, College of Life Sciences, Kyung Hee University, Gyeonggi-do 17104, Republic of Korea.
authors.forename: Joo-Hyun
authors.initials: JH
authors.lastname: Pi
authors.affiliation: From the Department of Genetic Engineering, College of Life Sciences, Kyung Hee University, Gyeonggi-do 17104, Republic of Korea cjkang@khu.ac.kr.
authors.forename: Chang-Joong
authors.initials: CJ
authors.lastname: Kang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D050657:Core Binding Factor alpha Subunits / Q000235:genetics / Q000378:metabolism*; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D054444:Immunoglobulin Light Chains, Surrogate / Q000235:genetics* / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009534:Niclosamide / Q000494:pharmacology; D054420:Pre-B Cell Receptors / Q000235:genetics / Q000378:metabolism; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; C493693:Cbfb protein, mouse; D050657:Core Binding Factor alpha Subunits; D050658:Core Binding Factor beta Subunit; C435748:Crlz1 protein, mouse; D004268:DNA-Binding Proteins; D006575:Heterocyclic Compounds, 3-Ring; D054444:Immunoglobulin Light Chains, Surrogate; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D009419:Nerve Tissue Proteins; D054420:Pre-B Cell Receptors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C544261:XAV939; D051176:beta Catenin; D009534:Niclosamide; D018021:Lithium Chloride
keywords: CBF&β; Crlz-1; Runx; Wnt signaling; beta-catenin (B-catenin); cell proliferation; immunology; lymphocyte; pre-B cell