miRNAs Are Essential for the Regulation of the PI3K/AKT/FOXO Pathway and Receptor Editing during B Cell Maturation
| Autor: | Doron Melamed, Sofia Bajwa, Tirtha Chakraborty, Marcus J. Hines, Gregg J. Silverman, Robert Blelloch, Lili Blumenberg, Lelise Getu, Mark M.W. Chong, Dinis Pedro Calado, Jane A. Skok, Sergei B. Koralov, Valentina Snetkova, David Benhamou, Maryaline Coffre, Kari Jensen, Dan R. Littman, Klaus Rajewsky, David Rieß |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Ribonuclease III Cancer Research PTEN Cellular differentiation Cell Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Receptors B cell development Transgenes B-Lymphocytes RNA-Binding Proteins Cell Differentiation Forkhead Transcription Factors medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis Antigen RNA Interference Signal transduction Signal Transduction Receptors Antigen B-Cell Down-Regulation Biology General Biochemistry Genetics and Molecular Biology Article Drosha DGCR8 03 medical and health sciences microRNA medicine Animals Protein kinase B PI3K/AKT/mTOR pathway B cell miRNA PI3K/AKT B-Cell receptor editing Receptor editing RAG MicroRNAs 030104 developmental biology Gene Expression Regulation Cancer research Immunoglobulin Light Chains RNA Editing Biochemistry and Cell Biology Proto-Oncogene Proteins c-akt Spleen B lymphocytes Dicer |
| Zdroj: | Coffre, M; Benhamou, D; Rieß, D; Blumenberg, L; Snetkova, V; Hines, MJ; et al.(2016). miRNAs Are Essential for the Regulation of the PI3K/AKT/FOXO Pathway and Receptor Editing during B Cell Maturation. Cell Reports, 17(9), 2271-2285. doi: 10.1016/j.celrep.2016.11.006. Lawrence Berkeley National Laboratory: Lawrence Berkeley National Laboratory. Retrieved from: http://www.escholarship.org/uc/item/4ks9128q Cell reports, vol 17, iss 9 Cell Reports |
| DOI: | 10.1016/j.celrep.2016.11.006. |
| Popis: | © 2016 The Author(s) B cell development is a tightly regulated process dependent on sequential rearrangements of immunoglobulin loci that encode the antigen receptor. To elucidate the role of microRNAs (miRNAs) in the orchestration of B cell development, we ablated all miRNAs at the earliest stage of B cell development by conditionally targeting the enzymes critical for RNAi in early B cell precursors. Absence of any one of these enzymes led to a block at the pro- to pre-B cell transition due to increased apoptosis and a failure of pre-B cells to proliferate. Expression of a Bcl2 transgene allowed for partial rescue of B cell development, however, the majority of the rescued B cells had low surface immunoglobulin expression with evidence of ongoing light chain editing. Our analysis revealed that miRNAs are critical for the regulation of the PTEN-AKT-FOXO1 pathway that in turn controls Rag expression during B cell development. |
| Databáze: | OpenAIRE |
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