Article: Identification of protein domains required for makorin-2-mediated neurogenesis inhibition in Xenopus embryos

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TitleIdentification of protein domains required for makorin-2-mediated neurogenesis inhibition in Xenopus embryos
AuthorsCheung, WKC1
Yang, PH1 3
Huang, QH2
Chen, Z2
Chen, SJ2
Lin, MCM1
Kung, HF3
KeywordsEmbryonic development
Makorin-2
Neurogenesis
Ribonucleoprotein
Zinc finger
Issue Date2010
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description
CitationBiochemical And Biophysical Research Communications, 2010, v. 394 n. 1, p. 18-23 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.bbrc.2010.02.041
AbstractMakorin-2, consisting of four highly conserved C3H zinc fingers, a Cys-His motif and a C3HC4 RING zinc finger domain, is a putative ribonucleoprotein. We have previously reported that Xenopus makorin-2 (mkrn2) is a neurogenesis inhibitor acting upstream of glycogen synthase kinase-3β (GSK-3β) in the phosphatidylinositol 3-kinase/Akt pathway. In an effort to identify the functional domains required for its anti-neurogenic activity, we designed and constructed a series of N- and C-terminal truncation mutants of mkrn2. Concurred with the full-length mkrn2, we showed that overexpression of one of the truncation mutants mkrn2(s)-7, which consists of only the third C3H zinc finger, Cys-His motif and C3HC4 RING zinc finger, is essential and sufficient to produce the phenotypical dorso-posterior deficiencies and small-head/short-tail phenotype in tadpoles. In animal cap explant assay, we further demonstrated that mkrn2(s)-7 not only inhibits activin and retinoic acid-induced animal cap neuralization and the expression of a pan-neural marker neural cell adhesion molecule, but also induces GSK-3β expression. These results collectively suggest that the third C3H zinc finger, Cys-His motif and C3HC4 RING zinc finger are indispensable for the anti-neurogenic activity of mkrn2. © 2010 Elsevier Inc. All rights reserved.
ISSN0006-291X
2011 Impact Factor: 2.484
2011 SCImago Journal Rankings: 0.287
DOIhttp://dx.doi.org/10.1016/j.bbrc.2010.02.041
ISI Accession Number IDWOS:000276474800004
Funding AgencyGrant Number
Research Grants Council of Hong Kong, ChinaN_CUHK721/03
CUHK7328/04M
National Natural Science Fund of China30318001
30200112
Funding Information:

We thank Prof. Ting-Xi Liu for critical review of the manuscript. This work was supported by Grants from the Research Grants Council of Hong Kong, China (N_CUHK721/03 and CUHK7328/04M) and National Natural Science Fund of China (30318001 and 30200112).

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorCheung, WKC
dc.contributor.authorYang, PH
dc.contributor.authorHuang, QH
dc.contributor.authorChen, Z
dc.contributor.authorChen, SJ
dc.contributor.authorLin, MCM
dc.contributor.authorKung, HF
dc.date.accessioned2010-09-06T06:17:36Z
dc.date.available2010-09-06T06:17:36Z
dc.date.issued2010
dc.description.abstractMakorin-2, consisting of four highly conserved C3H zinc fingers, a Cys-His motif and a C3HC4 RING zinc finger domain, is a putative ribonucleoprotein. We have previously reported that Xenopus makorin-2 (mkrn2) is a neurogenesis inhibitor acting upstream of glycogen synthase kinase-3β (GSK-3β) in the phosphatidylinositol 3-kinase/Akt pathway. In an effort to identify the functional domains required for its anti-neurogenic activity, we designed and constructed a series of N- and C-terminal truncation mutants of mkrn2. Concurred with the full-length mkrn2, we showed that overexpression of one of the truncation mutants mkrn2(s)-7, which consists of only the third C3H zinc finger, Cys-His motif and C3HC4 RING zinc finger, is essential and sufficient to produce the phenotypical dorso-posterior deficiencies and small-head/short-tail phenotype in tadpoles. In animal cap explant assay, we further demonstrated that mkrn2(s)-7 not only inhibits activin and retinoic acid-induced animal cap neuralization and the expression of a pan-neural marker neural cell adhesion molecule, but also induces GSK-3β expression. These results collectively suggest that the third C3H zinc finger, Cys-His motif and C3HC4 RING zinc finger are indispensable for the anti-neurogenic activity of mkrn2. © 2010 Elsevier Inc. All rights reserved.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationBiochemical And Biophysical Research Communications, 2010, v. 394 n. 1, p. 18-23 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.bbrc.2010.02.041
dc.identifier.doihttp://dx.doi.org/10.1016/j.bbrc.2010.02.041
dc.identifier.epage23
dc.identifier.hkuros168999
dc.identifier.isiWOS:000276474800004
Funding AgencyGrant Number
Research Grants Council of Hong Kong, ChinaN_CUHK721/03
CUHK7328/04M
National Natural Science Fund of China30318001
30200112
Funding Information:

We thank Prof. Ting-Xi Liu for critical review of the manuscript. This work was supported by Grants from the Research Grants Council of Hong Kong, China (N_CUHK721/03 and CUHK7328/04M) and National Natural Science Fund of China (30318001 and 30200112).

dc.identifier.issn0006-291X
2011 Impact Factor: 2.484
2011 SCImago Journal Rankings: 0.287
dc.identifier.issue1
dc.identifier.openurl
dc.identifier.pmid20167204
dc.identifier.scopuseid_2-s2.0-77949874355
dc.identifier.spage18
dc.identifier.urihttp://hdl.handle.net/10722/69872
dc.identifier.volume394
dc.languageeng
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description
dc.publisher.placeUnited States
dc.relation.ispartofBiochemical and Biophysical Research Communications
dc.relation.referencesReferences in Scopus
dc.subject.meshAmino Acid Motifs - genetics
dc.subject.meshNeurogenesis
dc.subject.meshRibonucleoproteins - classification - genetics - metabolism
dc.subject.meshXenopus Proteins - classification - genetics - metabolism
dc.subject.meshXenopus laevis - embryology - genetics - metabolism
dc.subjectEmbryonic development
dc.subjectMakorin-2
dc.subjectNeurogenesis
dc.subjectRibonucleoprotein
dc.subjectZinc finger
dc.titleIdentification of protein domains required for makorin-2-mediated neurogenesis inhibition in Xenopus embryos
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Shanghai Jiaotong University
  3. Chinese University of Hong Kong