Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8303943 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2013 | 10 Pages |
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+/CD19â 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+/CD19â and 2) zinc finger protein Zfp423 and peroxisome proliferator-activated receptor gamma (Pparg) in IgG1+/CD19+ splenocytes. In Aldh1a1â/â mice, splenic IgG1+/CD19â 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.
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Authors
R. Yasmeen, J.M. Meyers, C.E. Alvarez, J.L. Thomas, A. Bonnegarde-Bernard, H. Alder, T.L. Papenfuss, D.M. Jr., P.N. Boyaka, O. Ziouzenkova,