Table of Contents
To view the fulltext, log-in or choose pay-per-view options:
Get Access

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 Acta Haematol 2009;122:230–237 (DOI:10.1159/000253591)


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.


Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50