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J Biol Chem
2008 Mar 28;28313:8486-95. doi: 10.1074/jbc.M704768200.
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Makorin-2 is a neurogenesis inhibitor downstream of phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signal.
Yang PH
,
Cheung WK
,
Peng Y
,
He ML
,
Wu GQ
,
Xie D
,
Jiang BH
,
Huang QH
,
Chen Z
,
Lin MC
,
Kung HF
.
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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-3beta (GSK-3beta)-induced, neural cell adhesion molecule expression, indicating that mkrn2 acts downstream of PI3K and Akt and upstream of GSK-3beta. Moreover, mkrn2 up-regulated the mRNA and protein levels of GSK-3beta. 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.
Baker,
Wnt signaling in Xenopus embryos inhibits bmp4 expression and activates neural development.
1999, Pubmed,
Xenbase
Baker,
Wnt signaling in Xenopus embryos inhibits bmp4 expression and activates neural development.
1999,
Pubmed
,
Xenbase
Blom,
Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence.
2004,
Pubmed
Chang,
Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase.
1997,
Pubmed
Cross,
Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.
,
Pubmed
,
Xenbase
De,
Identification of four CCCH zinc finger proteins in Xenopus, including a novel vertebrate protein with four zinc fingers and severely restricted expression.
1999,
Pubmed
,
Xenbase
Duronio,
Downstream signalling events regulated by phosphatidylinositol 3-kinase activity.
1998,
Pubmed
Gray,
Phylogenetic conservation of the makorin-2 gene, encoding a multiple zinc-finger protein, antisense to the RAF1 proto-oncogene.
2001,
Pubmed
Gray,
The ancient source of a distinct gene family encoding proteins featuring RING and C(3)H zinc-finger motifs with abundant expression in developing brain and nervous system.
2000,
Pubmed
Hemmati-Brivanlou,
Inhibition of activin receptor signaling promotes neuralization in Xenopus.
1994,
Pubmed
,
Xenbase
Hudson,
Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d.
2004,
Pubmed
Jiang,
An essential role of phosphatidylinositol 3-kinase in myogenic differentiation.
1998,
Pubmed
Jiang,
Myogenic signaling of phosphatidylinositol 3-kinase requires the serine-threonine kinase Akt/protein kinase B.
1999,
Pubmed
Jiang,
Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells.
2000,
Pubmed
Joazeiro,
RING finger proteins: mediators of ubiquitin ligase activity.
2000,
Pubmed
Khwaja,
Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway.
1997,
Pubmed
Kim,
Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT.
2005,
Pubmed
Kintner,
Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction.
1987,
Pubmed
,
Xenbase
Lai,
Evidence that tristetraprolin binds to AU-rich elements and promotes the deadenylation and destabilization of tumor necrosis factor alpha mRNA.
1999,
Pubmed
Maéno,
A truncated bone morphogenetic protein 4 receptor alters the fate of ventral mesoderm to dorsal mesoderm: roles of animal pole tissue in the development of ventral mesoderm.
1994,
Pubmed
,
Xenbase
Obenauer,
Scansite 2.0: Proteome-wide prediction of cell signaling interactions using short sequence motifs.
2003,
Pubmed
Omwancha,
Makorin RING finger protein 1 (MKRN1) has negative and positive effects on RNA polymerase II-dependent transcription.
2006,
Pubmed
Peng,
Phosphatidylinositol 3-kinase signaling is involved in neurogenesis during Xenopus embryonic development.
2004,
Pubmed
,
Xenbase
Stern,
Neural induction: old problem, new findings, yet more questions.
2005,
Pubmed
,
Xenbase
Suzuki,
A truncated bone morphogenetic protein receptor affects dorsal-ventral patterning in the early Xenopus embryo.
1994,
Pubmed
,
Xenbase
Umbhauer,
Signaling specificities of fibroblast growth factor receptors in early Xenopus embryo.
2000,
Pubmed
,
Xenbase
Vivanco,
The phosphatidylinositol 3-Kinase AKT pathway in human cancer.
2002,
Pubmed
Vogt,
PI 3-kinase, mTOR, protein synthesis and cancer.
2001,
Pubmed
Wymann,
Phosphoinositide 3-kinase in disease: timing, location, and scaffolding.
2005,
Pubmed
Xu,
A dominant negative bone morphogenetic protein 4 receptor causes neuralization in Xenopus ectoderm.
1995,
Pubmed
,
Xenbase
Zhang,
Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.
2000,
Pubmed
