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Vol. 122, No. 4, 2009
Issue release date: November 2009
Section title: Original Paper
Acta Haematol 2009;122:230–237
(DOI:10.1159/000253591)

Sustained Expression of GRAIL during Hematopoiesis Results in Dysregulated Differentiation

MacKenzie D.A. · Seroogy C.M.
Division of Allergy/Immunology/Rheumatology, Department of Pediatrics, University of Wisconsin, Madison, Wisc., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 5/8/2009
Accepted: 8/12/2009
Published online: 10/30/2009

Number of Print Pages: 8
Number of Figures: 5
Number of Tables: 0

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: http://www.karger.com/AHA

Abstract

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.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 5/8/2009
Accepted: 8/12/2009
Published online: 10/30/2009

Number of Print Pages: 8
Number of Figures: 5
Number of Tables: 0

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: http://www.karger.com/AHA


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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