| Literature DB >> 24080087 |
R Yasmeen1, J M Meyers1, C E Alvarez2, J L Thomas1, A Bonnegarde-Bernard3, H Alder4, T L Papenfuss3, D M Benson5, P N Boyaka3, O Ziouzenkova6.
Abstract
The deregulation of B cell differentiation has been shown to contribute to autoimmune disorders, hematological cancers, and aging. We provide evidence that the retinoic acid-producing enzyme aldehyde dehydrogenase 1a1 (Aldh1a1) is an oncogene suppressor in specific splenic IgG1(+)/CD19(-) and IgG1(+)/CD19(+) B cell populations. Aldh1a1 regulated transcription factors during B cell differentiation in a sequential manner: 1) retinoic acid receptor alpha (Rara) in IgG1(+)/CD19(-) and 2) zinc finger protein Zfp423 and peroxisome proliferator-activated receptor gamma (Pparg) in IgG1(+)/CD19(+) splenocytes. In Aldh1a1(-/-) mice, splenic IgG1(+)/CD19(-) and IgG1(+)/CD19(+) B cells acquired expression of proto-oncogenic genes c-Fos, c-Jun, and Hoxa10 that resulted in splenomegaly. Human multiple myeloma B cell lines also lack Aldh1a1 expression; however, ectopic Aldh1a1 expression rescued Rara and Znf423 expressions in these cells. Our data highlight a mechanism by which an enzyme involved in vitamin A metabolism can improve B cell resistance to oncogenesis.Entities:
Keywords: AP1; Aldh1a1; Homeobox transcription factor; Hoxa10; Ig; Multiple myeloma; Nuclear receptor; Pparg; RA; RARE; Raldh1; Rara; Retinaldehyde; Vitamin A metabolism; Zfp423; Znf423; activator protein 1 a heterodimeric transcription factor formed by c-jun and c-fos; aldehyde dehydrogenase 1a1; c-Fos; c-Jun; human zinc finger protein; immunoglobulin; murine zinc finger protein; peroxisome proliferator-activated receptor; protein encoded by c-Jun gene; retinoic acid; retinoic acid receptor alpha; retinoic acid receptor response element; transcription factor encoded by the FOS gene; transcription factor homeobox protein a10
Mesh：
Substances：
Year: 2013 PMID： 24080087 PMCID： PMC3853404 DOI： 10.1016/j.bbamcr.2013.09.012
Source DB: PubMed Journal: Biochim Biophys Acta ISSN： 0006-3002