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Blood, 1 January 2007, Vol. 109, No. 1, pp. 100-108. Prepublished online as a Blood First Edition Paper on August 3, 2006; DOI 10.1182/blood-2006-02-003590. This Article Full Text (PDF) All Versions of this Article: blood-2006-02-003590v1 109/1/100    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Marteijn, J. A.F. Articles by van der Reijden, B. A. Search for Related Content PubMed PubMed Citation Articles by Marteijn, J. A.F. Articles by van der Reijden, B. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 13, 2006 Accepted June 22, 2006 Diminished proteasomal degradation results in accumulation of Gfi1 protein levels in monocytes Jurgen A.F. Marteijn, Laurens T. van der Meer, Liesbeth van Emst, Theo de Witte, Joop H. Jansen, and Bert A. van der Reijden* Central Hematology Laboratory, Radboud University Nijmegen, Nijmegen, The Netherlands * Corresponding author; email: b.vanderreijden{at}chl.umcn.nl. Gfi1 is a transcriptional repressor essential during myeloid differentiation. Gfi1-/- mice exhibit a block in myeloid differentiation resulting in the accumulation of an immature myelo-monocytic cell population and the complete absence of mature neutrophils. Even though mRNA levels of Gfi1 appear to be very low in monocytes, Gfi1 might play a role in the monocytic lineage as Gfi1-/- mice exhibit diminished monocyte-derived dendritic cells and disturbed cytokine production by macrophages in response to LPS. We show here that Gfi1 protein levels are mainly regulated by the ubiquitin-proteasome system. Upon forced monocytic differentiation of U937 cells Gfi1 mRNA levels dropped but protein levels increased due to diminished proteasomal turnover. Similarly, Gfi1 mRNA levels are low in primary monocytes while the protein is clearly detectable. Conversely, Gfi1 mRNA levels are high in granulocytes but the protein is swiftly degraded by the proteasome in these cells. Chromatin immunoprecipitation experiments showed that Gfi1 binds to the promoter of several granulocytic specific genes in primary monocytes, including C/EBP, neutrophil elastase and Gfi1 itself. The binding of the repressor Gfi1 to these promoters correlated with low expression of these genes in monocytes compared to granulocytes. Our data fit a model in which Gfi1 protein levels are induced in primary monocytes, due to diminished proteasomal degradation, to repress genes that play a role in granulocytic differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Yokomizo and E. Dzierzak Fine-tuning of hematopoietic stem cell homeostasis: novel role for ubiquitin ligase Genes & Dev., April 15, 2008; 22(8): 960 - 963. [Abstract] [Full Text] [PDF] J. A. F. Marteijn, L. T. van der Meer, L. van Emst, S. van Reijmersdal, W. Wissink, T. de Witte, J. H. Jansen, and B. A. Van der Reijden Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1 Blood, November 1, 2007; 110(9): 3128 - 3135. [Abstract] [Full Text] [PDF]

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