Sustained Expression of GRAIL during Hematopoiesis Results in Dysregulated DifferentiationMacKenzie D.A. · Seroogy C.M.
Division of Allergy/Immunology/Rheumatology, Department of Pediatrics, University of Wisconsin, Madison, Wisc., USA
Background/Aims: Despite a sophisticated understanding of the hematopoietic developmental program at the transcriptional level, our understanding of the role of E3 ubiquitin ligases remains underdeveloped. The E3 ubiquitin ligase, GRAIL (RNF128), is expressed in the bone marrow, but its role is as yet undefined. In this study, we evaluate the effect of GRAIL expression during hematopoietic differentiation in vitro and in vivo. Methods: Retroviral transduction of hematopoietic multipotent progenitor cells was used for methylcellulose colony assays and bone marrow reconstitution. Results: Enforced expression of GRAIL in colony assays demonstrated skewing of hematopoietic lineage development toward granulocytic/monocytic cells. Bone marrow reconstitution experiments with progenitor cells expressing biologically varied levels of GRAIL demonstrated diminished erythropoiesis and megakaryopoiesis if GRAIL (endogenous or forced) is maintained throughout hematopoiesis. Conclusion: These data highlight a role for GRAIL during hematopoiesis and emphasize the importance of studying posttranslational effects to complement our current understanding of the transcriptional regulation of hematopoiesis.
© 2009 S. Karger AG, Basel
Received: May 8, 2009
Accepted: August 12, 2009
Published online: October 30, 2009
Number of Print Pages : 8
Number of Figures : 5, Number of Tables : 0, Number of References : 22
Vol. 122, No. 4, Year 2009 (Cover Date: November 2009)
Journal Editor: Ben-Bassat I. (Qiryat-Ono)
ISSN: 0001-5792 (Print), eISSN: 1421-9662 (Online)
For additional information: http://www.karger.com/AHA