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

TitleIdentification of protein domains required for makorin-2-mediated neurogenesis inhibition in Xenopus embryos
Authors
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
Citation
Biochemical And Biophysical Research Communications, 2010, v. 394 n. 1, p. 18-23 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/69872
ISSN
2015 Impact Factor: 2.371
2015 SCImago Journal Rankings: 1.152
ISI Accession Number ID
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).

References

 

DC FieldValueLanguage
dc.contributor.authorCheung, WKCen_HK
dc.contributor.authorYang, PHen_HK
dc.contributor.authorHuang, QHen_HK
dc.contributor.authorChen, Zen_HK
dc.contributor.authorChen, SJen_HK
dc.contributor.authorLin, MCMen_HK
dc.contributor.authorKung, HFen_HK
dc.date.accessioned2010-09-06T06:17:36Z-
dc.date.available2010-09-06T06:17:36Z-
dc.date.issued2010en_HK
dc.identifier.citationBiochemical And Biophysical Research Communications, 2010, v. 394 n. 1, p. 18-23en_HK
dc.identifier.issn0006-291Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/69872-
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.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/descriptionen_HK
dc.relation.ispartofBiochemical and Biophysical Research Communicationsen_HK
dc.subjectEmbryonic developmenten_HK
dc.subjectMakorin-2en_HK
dc.subjectNeurogenesisen_HK
dc.subjectRibonucleoproteinen_HK
dc.subjectZinc fingeren_HK
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.titleIdentification of protein domains required for makorin-2-mediated neurogenesis inhibition in Xenopus embryosen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-291X&volume=394&issue=1&spage=18&epage=23&date=2010&atitle=Identification+of+Protein+Domains+Required+for+Makorin-2-mediated+Neurogenesis+Inhibition+in+Xenopus+Embryosen_HK
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_HK
dc.identifier.authorityLin, MCM=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bbrc.2010.02.041en_HK
dc.identifier.pmid20167204-
dc.identifier.scopuseid_2-s2.0-77949874355en_HK
dc.identifier.hkuros168999en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77949874355&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume394en_HK
dc.identifier.issue1en_HK
dc.identifier.spage18en_HK
dc.identifier.epage23en_HK
dc.identifier.isiWOS:000276474800004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCheung, WKC=35080070600en_HK
dc.identifier.scopusauthoridYang, PH=24340289000en_HK
dc.identifier.scopusauthoridHuang, QH=7403634376en_HK
dc.identifier.scopusauthoridChen, Z=26643572800en_HK
dc.identifier.scopusauthoridChen, SJ=13310288700en_HK
dc.identifier.scopusauthoridLin, MCM=7404816359en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK

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