Abstract:
:The Komeda miniature rat Ishikawa (KMI) is a naturally occurring mutant caused by an autosomal recessive mutation mri, which exhibits longitudinal growth retardation. Here we identified the mri mutation as a deletion in the rat gene encoding cGMP-dependent protein kinase type II (cGKII). KMIs showed an expanded growth plate and impaired bone healing with abnormal accumulation of postmitotic but nonhypertrophic chondrocytes. Ex vivo culture of KMI chondrocytes reproduced the differentiation impairment, which was restored by introducing the adenovirus-mediated cGKII gene. The expression of Sox9, an inhibitory regulator of hypertrophic differentiation, persisted in the nuclei of postmitotic chondrocytes of the KMI growth plate. Transfection experiments in culture systems revealed that cGKII attenuated the Sox9 functions to induce the chondrogenic differentiation and to inhibit the hypertrophic differentiation of chondrocytes. This attenuation of Sox9 was due to the cGKII inhibition of nuclear entry of Sox9. The impaired differentiation of cultured KMI chondrocytes was restored by the silencing of Sox9 through RNA interference. Hence, the present study for the first time shed light on a novel role of cGKII as a molecular switch, coupling the cessation of proliferation and the start of hypertrophic differentiation of chondrocytes through attenuation of Sox9 function.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Chikuda H,Kugimiya F,Hoshi K,Ikeda T,Ogasawara T,Shimoaka T,Kawano H,Kamekura S,Tsuchida A,Yokoi N,Nakamura K,Komeda K,Chung UI,Kawaguchi Hdoi
10.1101/gad.1224204subject
Has Abstractpub_date
2004-10-01 00:00:00pages
2418-29issue
19eissn
0890-9369issn
1549-5477pii
18/19/2418journal_volume
18pub_type
杂志文章abstract::The mechanisms by which homeoproteins bind selectively to target genes in vivo have long remained unresolved. Here we report that PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein by regulating its subnuclear localization and proximity to target genes. We demonstrate that the interaction of Msx1 with PIAS...
journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.12.1519
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 评论,杂志文章
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更新日期:2011-05-01 00:00:00
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.6.698
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journal_title:Genes & development
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更新日期:2001-02-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1996-02-15 00:00:00
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journal_title:Genes & development
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更新日期:1999-08-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1996-08-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1995-08-15 00:00:00
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2000-06-15 00:00:00
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journal_title:Genes & development
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abstract::Plectin, a major linker and scaffolding protein of the cytoskeleton, has been shown to be essential for the mechanical integrity of skin, skeletal muscle, and heart. Studying fibroblast and astroglial cell cultures derived from plectin (-/-) mice, we found that their actin cytoskeleton, including focal adhesion contac...
journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1998-11-01 00:00:00
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journal_title:Genes & development
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journal_title:Genes & development
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更新日期:2005-08-15 00:00:00
abstract::Transcription factor p53 forms a network with associated factors to regulate the cell cycle and apoptosis in response to environmental stresses. However, there is currently no direct genetic evidence to show if or how the p53 pathway functions during organogenesis. Here we present evidence to show that the zebrafish d...
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更新日期:2005-12-01 00:00:00