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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3128-3135. Prepublished online as a Blood First Edition Paper on July 23, 2007; DOI 10.1182/blood-2006-11-058602. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2006-11-058602v1 110/9/3128    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 November 29, 2006 Accepted July 20, 2007 Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1 Jurgen A.F. Marteijn, Laurens T van der Meer, Liesbeth van Emst, Simon van Reijmersdal, Willemijn Wissink, Theo de Witte, Joop H Jansen, and Bert A. Van der Reijden* Central Hematology Laboratory, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen, Netherlands Department of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen, Netherlands * Corresponding author; email: b.vanderreijden{at}chl.umcn.nl. Growth factor independence 1 (Gfi1) is a transcriptional repressor essential for the function and development of many different hematopoietic lineages. The Gfi1 protein expression is regulated by the ubiquitin-proteasome system. In granulocytes Gfi1 is rapidly degraded by the proteasome, while it is more stable in monocytes. How the ubiquitination and degradation of Gfi1 is regulated is unclear. Here we show that the ubiquitin ligase Triad1 interacts with the DNA binding domain of Gfi1. Unexpectedly, we found that Triad1 inhibited Gfi1 ubiquitination resulting in a prolonged half-life. Downregulation of endogenous Triad1 by siRNAs resulted in increased Gfi1 ubiquitination. In U937 cells, Triad1 caused an increase in endogenous Gfi1 protein levels and slowed cell proliferation in a similar manner when Gfi1 itself was expressed. A Triad1 mutant that lacks the Gfi1 binding domain did not affect Gfi1 levels and proliferation. Because neither proteasome- nor Triad1 ubiquitin ligase activity was required for the inhibition of Gfi1 ubiquitination, these data suggest that Triad1 competes for Gfi1 binding with as yet to be identified E3 ubiquitin ligases that do mark Gfi1 for proteasomal degradation. The fine-tuning of Gfi1 protein levels regulated by Triad1 defines an unexpected role for this protein in hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. A. Marteijn, S. Bekker-Jensen, N. Mailand, H. Lans, P. Schwertman, A. M. Gourdin, N. P. Dantuma, J. Lukas, and W. Vermeulen Nucleotide excision repair-induced H2A ubiquitination is dependent on MDC1 and RNF8 and reveals a universal DNA damage response J. Cell Biol., September 21, 2009; 186(6): 835 - 847. [Abstract] [Full Text] [PDF] A. Ehrlund, E. H. Anthonisen, N. Gustafsson, N. Venteclef, K. Robertson Remen, A. E. Damdimopoulos, A. Galeeva, M. Pelto-Huikko, E. Lalli, K. R. Steffensen, et al. E3 Ubiquitin Ligase RNF31 Cooperates with DAX-1 in Transcriptional Repression of Steroidogenesis Mol. Cell. Biol., April 15, 2009; 29(8): 2230 - 2242. [Abstract] [Full Text] [PDF] R. Shinnakasu, M. Yamashita, M. Kuwahara, H. Hosokawa, A. Hasegawa, S. Motohashi, and T. Nakayama Gfi1-mediated Stabilization of GATA3 Protein Is Required for Th2 Cell Differentiation J. Biol. Chem., October 17, 2008; 283(42): 28216 - 28225. [Abstract] [Full Text] [PDF]

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