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

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TitleMakorin-2 is a neurogenesis inhibitor downstream of phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signal
AuthorsYang, PH1 3 5
Cheung, WKC1
Peng, Y3
He, ML3 5
Wu, GQ1 3 5
Xie, D3 5
Jiang, BH2
Huang, QH4
Chen, Z2
Lin, MCM1
Kung, HF3 5
Issue Date2008
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
CitationJournal Of Biological Chemistry, 2008, v. 283 n. 13, p. 8486-8495 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M704768200
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.
ISSN0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
DOIhttp://dx.doi.org/10.1074/jbc.M704768200
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorYang, PH
dc.contributor.authorCheung, WKC
dc.contributor.authorPeng, Y
dc.contributor.authorHe, ML
dc.contributor.authorWu, GQ
dc.contributor.authorXie, D
dc.contributor.authorJiang, BH
dc.contributor.authorHuang, QH
dc.contributor.authorChen, Z
dc.contributor.authorLin, MCM
dc.contributor.authorKung, HF
dc.date.accessioned2012-10-08T03:17:14Z
dc.date.available2012-10-08T03:17:14Z
dc.date.issued2008
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.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationJournal Of Biological Chemistry, 2008, v. 283 n. 13, p. 8486-8495 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M704768200
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M704768200
dc.identifier.epage8495
dc.identifier.issn0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
dc.identifier.issue13
dc.identifier.scopuseid_2-s2.0-43749109183
dc.identifier.spage8486
dc.identifier.urihttp://hdl.handle.net/10722/168299
dc.identifier.volume283
dc.languageeng
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
dc.publisher.placeUnited States
dc.relation.ispartofJournal of Biological Chemistry
dc.relation.referencesReferences in Scopus
dc.titleMakorin-2 is a neurogenesis inhibitor downstream of phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signal
dc.typeArticle
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