Sustained expression of GRAIL during hematopoiesis results in dysregulated differentiation.
OBJECTIVE
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.


CONCLUSIONS
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.
MacKenzie
Debra A
DA
Division of Allergy/Immunology/Rheumatology, Department of Pediatrics, University of Wisconsin, Madison, WI., USA.
Seroogy
Christine M
CM
D000818:Animals; D002454:Cell Differentiation; D004920:Erythropoiesis; D015870:Gene Expression; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D039902:Multipotent Stem Cells / Q000166:cytology / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011828:Radiation Chimera; D011994:Recombinant Proteins / Q000235:genetics; D034061:Thrombopoiesis; D014161:Transduction, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D012333:RNA, Messenger; D011994:Recombinant Proteins; C520250:RNF128 protein, human; D044767:Ubiquitin-Protein Ligases