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Conference Paper: The Role of Methionine Aminopeptidase II in Definitive Hematopoiesis in Zebrafish Embryos

TitleThe Role of Methionine Aminopeptidase II in Definitive Hematopoiesis in Zebrafish Embryos
Authors
Issue Date2010
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/exphem
Citation
The 39th Annual Scientific Meeting of the International Society for Experimental Hematology (ISEH 2010), Melbourne, Australia, 15-18 September 2010. In Experimental Hematology, 2010, v. 38 n. 9 suppl., p. S1-S2, abstract no. 003 How to Cite?
AbstractObjective: Methionine aminopeptidase 2 (Metap2) is the target of anti-angiogenic compound fumagillin and has been investigated for its expression in cancers and its antiproliferative effects on endothelial cells. It is a protease which removes N-terminal methionine from newly synthesized peptides and also the eIF- 2 associated 67 kDa protein (p67), which prevents phosphorylation of eIFα and ERK1/2, fine-tuning cellular protein synthesis and proliferation. However, the role of Metap2 during embryonic development remained unclear. Here, we used zebrafish model to investigate the role of metap2 during embryonic development, with particular reference to definitive hematopoiesis. Methods and Results: We injected morpholino targeting the splice-junction of metap2 into zebrafish embryos (referred as metap2MO embryos). Molecular targeting was confirmed by RT-PCR. Modulation of metap2 activity was shown by shifting of the gapdh isoelectric point. The metap2MO embryos exhibited significant upregulation of definitive hematopoietic genes (cmyb and runx1) as shown by both in-situ hybridization and real-time PCR at 36 hour-postfertilization. The phenotype could be rescued by co-injecting the embryos with metap2 mRNA and re-capitulated by treating the embryos with fumagillin. Mechanistically, metap2MO embryos shows ectopic erk1/2 phosphorylation and the hematopoietic phenotypes could be rescued by treating embryos with ERK inhibitors. The metap2MO embryos also exhibited reduced camodulin kinase 2 (camk2) activity and the hematopoietic phenotypes could also be rescued by camk2 mRNA and recapitulated by a CaMK2 inhibitor. The canonical Wnt pathway, characterized by
DescriptionPoster Presentation
Persistent Identifierhttp://hdl.handle.net/10722/190071
ISSN
2015 Impact Factor: 2.303
2015 SCImago Journal Rankings: 1.341

 

DC FieldValueLanguage
dc.contributor.authorMa, CHen_US
dc.contributor.authorLin, Hen_US
dc.contributor.authorChung, ISen_US
dc.contributor.authorYang, Den_US
dc.contributor.authorLiang, RHSen_US
dc.contributor.authorLeung, AYHen_US
dc.date.accessioned2013-09-17T15:06:26Z-
dc.date.available2013-09-17T15:06:26Z-
dc.date.issued2010en_US
dc.identifier.citationThe 39th Annual Scientific Meeting of the International Society for Experimental Hematology (ISEH 2010), Melbourne, Australia, 15-18 September 2010. In Experimental Hematology, 2010, v. 38 n. 9 suppl., p. S1-S2, abstract no. 003en_US
dc.identifier.issn0301-472X-
dc.identifier.urihttp://hdl.handle.net/10722/190071-
dc.descriptionPoster Presentation-
dc.description.abstractObjective: Methionine aminopeptidase 2 (Metap2) is the target of anti-angiogenic compound fumagillin and has been investigated for its expression in cancers and its antiproliferative effects on endothelial cells. It is a protease which removes N-terminal methionine from newly synthesized peptides and also the eIF- 2 associated 67 kDa protein (p67), which prevents phosphorylation of eIFα and ERK1/2, fine-tuning cellular protein synthesis and proliferation. However, the role of Metap2 during embryonic development remained unclear. Here, we used zebrafish model to investigate the role of metap2 during embryonic development, with particular reference to definitive hematopoiesis. Methods and Results: We injected morpholino targeting the splice-junction of metap2 into zebrafish embryos (referred as metap2MO embryos). Molecular targeting was confirmed by RT-PCR. Modulation of metap2 activity was shown by shifting of the gapdh isoelectric point. The metap2MO embryos exhibited significant upregulation of definitive hematopoietic genes (cmyb and runx1) as shown by both in-situ hybridization and real-time PCR at 36 hour-postfertilization. The phenotype could be rescued by co-injecting the embryos with metap2 mRNA and re-capitulated by treating the embryos with fumagillin. Mechanistically, metap2MO embryos shows ectopic erk1/2 phosphorylation and the hematopoietic phenotypes could be rescued by treating embryos with ERK inhibitors. The metap2MO embryos also exhibited reduced camodulin kinase 2 (camk2) activity and the hematopoietic phenotypes could also be rescued by camk2 mRNA and recapitulated by a CaMK2 inhibitor. The canonical Wnt pathway, characterized by-
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/exphem-
dc.relation.ispartofExperimental Hematologyen_US
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Experimental Hematology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Experimental Hematology, 2010, v. 38 n. 9 Suppl., p. S1-S2, abstract no. 003-
dc.titleThe Role of Methionine Aminopeptidase II in Definitive Hematopoiesis in Zebrafish Embryosen_US
dc.typeConference_Paperen_US
dc.identifier.emailMa, CH: alvinma@hku.hken_US
dc.identifier.emailLiang, RHS: rliang@hku.hken_US
dc.identifier.emailLeung, AYH: ayhleung@hku.hken_US
dc.identifier.authorityMa, CH=rp01810en_US
dc.identifier.authorityLiang, RHS=rp00345en_US
dc.identifier.hkuros224788en_US
dc.identifier.volume38-
dc.identifier.issue9 suppl.-
dc.identifier.spageS1, abstract no. 003-
dc.identifier.epageS2-
dc.publisher.placeUnited States-

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