Zfp521 promotes B-cell viability and cyclin D1 gene expression in a B cell culture system.
Leukemia arises due to the dysregulated proliferation of hematopoietic progenitor cells. Errors in the multi-step commitment process result in excessive numbers of immature lymphocytes, causing malignant disease. Genes involved in the differentiation of lymphocytes are often associated with leukemia. One such gene, Zfp521, has been found to cause B-cell leukemia in mice when over-expressed. The role of Zfp521 in B-cell differentiation, and the mechanisms by which it leads to leukemic transformation, are unclear. In this study we report that Zfp521 knockdown causes apoptosis in a B-cell culture system and promotes down-regulation of genes acting at late stages of B-cell differentiation. We identify Pax5 and cyclin D1 as Zfp521 target genes, and suggest that excessive B-cell proliferation observed in mice with retroviral insertions near the Zfp521 gene is due to an up-regulation of cyclin D1 in B-cells. Overall, these results suggest links between dysregulated Zfp521 and B-cell survival.
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
Salma
S
Al Dallal
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
Kathryn
K
Wolton
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK. Electronic address: Kathryn.Hentges@manchester.ac.uk.
Kathryn E
KE
Hentges
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D051379:Mice; D051757:PAX5 Transcription Factor / Q000235:genetics*
D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C529598:zinc finger protein 521, human; D019938:Cyclin D1
Cyclin D1; Ebf1; Evi3; Pax5; Zfp423; Zfp521