Aldehyde dehydrogenase-1a1 induces oncogene suppressor genes in B cell populations.
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.
Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA.
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R
Yasmeen
Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA.
J M
JM
Meyers
Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
C E
CE
Alvarez
Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA.
J L
JL
Thomas
Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.
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A
Bonnegarde-Bernard
Nucleic Acid Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
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H
Alder
Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.
T L
TL
Papenfuss
Division of Hematology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
D M
DM
Benson
Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.
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PN
Boyaka
Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA. Electronic address: ziouzenkova.1@osu.edu.
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Ziouzenkova
D000444:Aldehyde Dehydrogenase / Q000172:deficiency / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D008954:Models, Biological; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D050697:Retinal Dehydrogenase; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013163:Splenomegaly / Q000276:immunology / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000378:metabolism
D018941:Antigens, CD19; D004268:DNA-Binding Proteins; C484557:Ebfaz protein, mouse; D047495:PPAR gamma; D014157:Transcription Factors; D014801:Vitamin A; D014212:Tretinoin; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase
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