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Article: Makorin-2 is a neurogenesis inhibitor downstream of phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signal

TitleMakorin-2 is a neurogenesis inhibitor downstream of phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signal
Authors
Issue Date2008
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2008, v. 283 n. 13, p. 8486-8495 How to Cite?
Abstract
Makorin-2 belongs to the makorin RING zinc finger gene family, which encodes putative ribonucleoproteins. Here we cloned the Xenopus makorin-2 (mkrn2) and characterized its function in Xenopus neurogenesis. Forced overexpression of mkrn2 produced tadpoles with dorso-posterior deficiencies and small-head/short-tail phenotype, whereas knockdown of mkrn2 by morpholino antisense oligonucleotides induced double axis in tadpoles. In Xenopus animal cap explant assay, mkrn2 inhibited activin, and retinoic acid induced animal cap neuralization, as evident from the suppression of a pan neural marker, neural cell adhesion molecule. Surprisingly, the anti-neurogenic activity of mkrn2 is independent of the two major neurogenesis signaling cascades, BMP-4 and Wnt8 pathways. Instead, mkrn2 works specifically through the phosphatidylinositol 3-kinase (PI3K) and Akt-mediated neurogenesis pathway. Overexpression of mkrn2 completely abrogated constitutively active PI3K- and Akt-induced, but not dominant negative glycogen synthase kinase-3β (GSK-3β)-induced, neural cell adhesion molecule expression, indicating that mkrn2 acts downstream of PI3K and Akt and upstream of GSK-3β. Moreover, mkrn2 up-regulated the mRNA and protein levels of GSK-3β. These results revealed for the first time the important role of mkrn2 as a new player in PI3K/Akt-mediated neurogenesis during Xenopus embryonic development. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/168299
ISSN
2013 Impact Factor: 4.600
ISI Accession Number ID
References

 

Author Affiliations
  1. Institute of Molecular Technology for Drug Discovery and Synthesis, Hong Kong
  2. Nanjing Medical University
  3. Sun Yat-Sen University
  4. Shanghai Second Medical University
  5. Chinese University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorYang, PHen_US
dc.contributor.authorCheung, WKCen_US
dc.contributor.authorPeng, Yen_US
dc.contributor.authorHe, MLen_US
dc.contributor.authorWu, GQen_US
dc.contributor.authorXie, Den_US
dc.contributor.authorJiang, BHen_US
dc.contributor.authorHuang, QHen_US
dc.contributor.authorChen, Zen_US
dc.contributor.authorLin, MCMen_US
dc.contributor.authorKung, HFen_US
dc.date.accessioned2012-10-08T03:17:14Z-
dc.date.available2012-10-08T03:17:14Z-
dc.date.issued2008en_US
dc.identifier.citationJournal Of Biological Chemistry, 2008, v. 283 n. 13, p. 8486-8495en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/168299-
dc.description.abstractMakorin-2 belongs to the makorin RING zinc finger gene family, which encodes putative ribonucleoproteins. Here we cloned the Xenopus makorin-2 (mkrn2) and characterized its function in Xenopus neurogenesis. Forced overexpression of mkrn2 produced tadpoles with dorso-posterior deficiencies and small-head/short-tail phenotype, whereas knockdown of mkrn2 by morpholino antisense oligonucleotides induced double axis in tadpoles. In Xenopus animal cap explant assay, mkrn2 inhibited activin, and retinoic acid induced animal cap neuralization, as evident from the suppression of a pan neural marker, neural cell adhesion molecule. Surprisingly, the anti-neurogenic activity of mkrn2 is independent of the two major neurogenesis signaling cascades, BMP-4 and Wnt8 pathways. Instead, mkrn2 works specifically through the phosphatidylinositol 3-kinase (PI3K) and Akt-mediated neurogenesis pathway. Overexpression of mkrn2 completely abrogated constitutively active PI3K- and Akt-induced, but not dominant negative glycogen synthase kinase-3β (GSK-3β)-induced, neural cell adhesion molecule expression, indicating that mkrn2 acts downstream of PI3K and Akt and upstream of GSK-3β. Moreover, mkrn2 up-regulated the mRNA and protein levels of GSK-3β. These results revealed for the first time the important role of mkrn2 as a new player in PI3K/Akt-mediated neurogenesis during Xenopus embryonic development. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.titleMakorin-2 is a neurogenesis inhibitor downstream of phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signalen_US
dc.typeArticleen_US
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_US
dc.identifier.authorityLin, MCM=rp00746en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1074/jbc.M704768200en_US
dc.identifier.pmid18198183-
dc.identifier.scopuseid_2-s2.0-43749109183en_US
dc.identifier.hkuros139939-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-43749109183&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume283en_US
dc.identifier.issue13en_US
dc.identifier.spage8486en_US
dc.identifier.epage8495en_US
dc.identifier.isiWOS:000254288000047-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYang, PH=24340289000en_US
dc.identifier.scopusauthoridCheung, WKC=35080070600en_US
dc.identifier.scopusauthoridPeng, Y=7403419265en_US
dc.identifier.scopusauthoridHe, ML=35080389700en_US
dc.identifier.scopusauthoridWu, GQ=7404976124en_US
dc.identifier.scopusauthoridXie, D=35070710200en_US
dc.identifier.scopusauthoridJiang, BH=35264238500en_US
dc.identifier.scopusauthoridHuang, QH=7403634376en_US
dc.identifier.scopusauthoridChen, Z=52963288600en_US
dc.identifier.scopusauthoridLin, MCM=7404816359en_US
dc.identifier.scopusauthoridKung, HF=7402514190en_US

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