Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes.

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 Dev

journal_title

Genes & development

authors

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 H

doi

10.1101/gad.1224204

subject

Has Abstract

pub_date

2004-10-01 00:00:00

pages

2418-29

issue

19

eissn

0890-9369

issn

1549-5477

pii

18/19/2418

journal_volume

18

pub_type

杂志文章
  • PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein.

    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

    doi:10.1101/gad.1392006

    authors: Lee H,Quinn JC,Prasanth KV,Swiss VA,Economides KD,Camacho MM,Spector DL,Abate-Shen C

    更新日期:2006-04-01 00:00:00

  • Brachyury downstream notochord differentiation in the ascidian embryo.

    abstract::The ascidian tadpole represents the most simplified chordate body plan. It contains a notochord composed of just 40 cells, but as in vertebrates Brachyury is essential for notochord differentiation. Here, we show that the misexpression of the Brachyury gene (Ci-Bra) of Ciona intestinalis is sufficient to transform end...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.13.12.1519

    authors: Takahashi H,Hotta K,Erives A,Di Gregorio A,Zeller RW,Levine M,Satoh N

    更新日期:1999-06-15 00:00:00

  • Nuclear myosin I acts in concert with polymeric actin to drive RNA polymerase I transcription.

    abstract::Actin is associated with all three nuclear RNA polymerases and acts in concert with nuclear myosin I (NM1) to drive transcription. Practically nothing is known regarding the state of actin and the functional interplay of actin and NM1 in transcription. Here we show that actin and NM1 act in concert to promote RNA poly...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.455908

    authors: Ye J,Zhao J,Hoffmann-Rohrer U,Grummt I

    更新日期:2008-02-01 00:00:00

  • Fragile X-related protein and VIG associate with the RNA interference machinery.

    abstract::RNA interference (RNAi) is a flexible gene silencing mechanism that responds to double-stranded RNA by suppressing homologous genes. Here, we report the characterization of RNAi effector complexes (RISCs) that contain small interfering RNAs and microRNAs (miRNAs). We identify two putative RNA-binding proteins, the Dro...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1025202

    authors: Caudy AA,Myers M,Hannon GJ,Hammond SM

    更新日期:2002-10-01 00:00:00

  • Addicted to Myc--but why?

    abstract::Many tumors continuously depend on the initiating oncogenes, but whether this extends to their downstream targets is unclear. In this issue of Genes & Development, Sodir and colleagues (pp. 907-916) demonstrate an essential role for endogenous Myc proteins in maintaining the tumor microenvironment, providing an unexpe...

    journal_title:Genes & development

    pub_type: 评论,杂志文章

    doi:10.1101/gad.2053311

    authors: von Eyss B,Eilers M

    更新日期:2011-05-01 00:00:00

  • GCN5 is a required cofactor for a ubiquitin ligase that targets NF-kappaB/RelA.

    abstract::The transcription factor NF-kappaB is a critical regulator of inflammatory and cell survival signals. Proteasomal degradation of NF-kappaB subunits plays an important role in the termination of NF-kappaB activity, and at least one of the identified ubiquitin ligases is a multimeric complex containing Copper Metabolism...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1748409

    authors: Mao X,Gluck N,Li D,Maine GN,Li H,Zaidi IW,Repaka A,Mayo MW,Burstein E

    更新日期:2009-04-01 00:00:00

  • Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break.

    abstract::The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae) control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and Tel2 interact, and that even when Tel1 protein levels are high, this interacti...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1646208

    authors: Anderson CM,Korkin D,Smith DL,Makovets S,Seidel JJ,Sali A,Blackburn EH

    更新日期:2008-04-01 00:00:00

  • Pcf11 orchestrates transcription termination pathways in yeast.

    abstract::In Saccharomyces cerevisiae, short noncoding RNA (ncRNA) generated by RNA polymerase II (Pol II) are terminated by the NRD complex consisting of Nrd1, Nab3, and Sen1. We now show that Pcf11, a component of the cleavage and polyadenylation complex (CPAC), is also generally required for NRD-dependent transcription termi...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.251470.114

    authors: Grzechnik P,Gdula MR,Proudfoot NJ

    更新日期:2015-04-15 00:00:00

  • Identification of in vivo mRNA targets of GLD-1, a maxi-KH motif containing protein required for C. elegans germ cell development.

    abstract::Caenorhabditis elegans GLD-1, a KH motif containing RNA-binding protein of the GSG/STAR subfamily, controls diverse aspects of germ line development, suggesting that it may have multiple mRNA targets. We used an immunoprecipitation/subtractive hybridization/cloning strategy to identify 15 mRNAs that are putative targe...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.915901

    authors: Lee MH,Schedl T

    更新日期:2001-09-15 00:00:00

  • The embryonic lethality of homozygous lethal yellow mice (Ay/Ay) is associated with the disruption of a novel RNA-binding protein.

    abstract::Lethal yellow (Ay) is a mutation at the mouse agouti (a) locus that is associated with an all-yellow coat color, obesity, diabetes, tumors in heterozygotes, and preimplantation embryonic lethality in homozygotes. Previously, we cloned and characterized the wild-type agouti gene and demonstrated that it expresses a 0.8...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.7.7a.1203

    authors: Michaud EJ,Bultman SJ,Stubbs LJ,Woychik RP

    更新日期:1993-07-01 00:00:00

  • Sex-specific regulation of the male-specific lethal-1 dosage compensation gene in Drosophila.

    abstract::Dosage compensation in Drosophila occurs by a twofold increase in transcription per copy of X-linked genes in males (XY) compared with females (XX). msl-1 is one of four genes that are essential for dosage compensation in males, and MSL-1 protein is associated specifically with the male X chromosome. To explore the ba...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.8.6.698

    authors: Palmer MJ,Richman R,Richter L,Kuroda MI

    更新日期:1994-03-15 00:00:00

  • mRNA 5'-leader trans-splicing in the chordates.

    abstract::We report the discovery of mRNA 5'-leader trans-splicing (SL trans-splicing) in the chordates. In the ascidian protochordate Ciona intestinalis, the mRNAs of at least seven genes undergo trans-splicing of a 16-nucleotide 5'-leader apparently derived from a 46-nucleotide RNA that shares features with previously charact...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.865401

    authors: Vandenberghe AE,Meedel TH,Hastings KE

    更新日期:2001-02-01 00:00:00

  • Transcription factor Spo0A switches the localization of the cell division protein FtsZ from a medial to a bipolar pattern in Bacillus subtilis.

    abstract::Entry into sporulation by the Gram-positive bacterium Bacillus subtilis is governed by two transcription factors, Spo0A and sigma H, and involves a switch in the site of division from a medial to a polar location. We report that at the onset of sporulation, assembly of the cell division protein FtsZ shifts from midcel...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.10.4.478

    authors: Levin PA,Losick R

    更新日期:1996-02-15 00:00:00

  • Bacterial promoter architecture: subsite structure of UP elements and interactions with the carboxy-terminal domain of the RNA polymerase alpha subunit.

    abstract::We demonstrate here that the previously described bacterial promoter upstream element (UP element) consists of two distinct subsites, each of which, by itself, can bind the RNA polymerase holoenzyme alpha subunit carboxy-terminal domain (RNAP alphaCTD) and stimulate transcription. Using binding-site-selection experime...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.13.16.2134

    authors: Estrem ST,Ross W,Gaal T,Chen ZW,Niu W,Ebright RH,Gourse RL

    更新日期:1999-08-15 00:00:00

  • Sequence-specific DNA binding of the B-cell-specific coactivator OCA-B.

    abstract::B-cell-specific transcription of immunoglobulin genes is mediated by the interaction of a POU domain containing transcription factor Oct-1 or Oct-2, with the B-cell-specific coactivator OCA-B (Bob-1, OBF-1) and a prototype octamer element. We find that OCA-B binds DNA directly in the major groove between the two subdo...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.10.16.2079

    authors: Cepek KL,Chasman DI,Sharp PA

    更新日期:1996-08-15 00:00:00

  • Pit-1 binding to specific DNA sites as a monomer or dimer determines gene-specific use of a tyrosine-dependent synergy domain.

    abstract::Transcriptional activation of the prolactin and growth hormone genes, occurring in a cell-specific fashion, requires short-range synergistic interactions between the pituitary-specific POU domain factor Pit-1 and other transcription factors, particularly nuclear receptors. Unexpectedly, we find that these events invol...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.9.16.1992

    authors: Holloway JM,Szeto DP,Scully KM,Glass CK,Rosenfeld MG

    更新日期:1995-08-15 00:00:00

  • Biological functions of the ISWI chromatin remodeling complex NURF.

    abstract::The nucleosome remodeling factor (NURF) is one of several ISWI-containing protein complexes that catalyze ATP-dependent nucleosome sliding and facilitate transcription of chromatin in vitro. To establish the physiological requirements of NURF, and to distinguish NURF genetically from other ISWI-containing complexes, w...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1032202

    authors: Badenhorst P,Voas M,Rebay I,Wu C

    更新日期:2002-12-15 00:00:00

  • Keratinocyte growth factor is required for hair development but not for wound healing.

    abstract::Keratinocyte growth factor (KGF), also known as fibroblast growth factor 7 (FGF7), is synthesized by skin fibroblasts. However, its mitogenic activity is on skin keratinocytes, where it is the most potent growth factor identified thus far. To explore KGF's function in vivo, we used embryonic stem cell technology to ge...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.10.2.165

    authors: Guo L,Degenstein L,Fuchs E

    更新日期:1996-01-15 00:00:00

  • A homeobox gene, PRESSED FLOWER, regulates lateral axis-dependent development of Arabidopsis flowers.

    abstract::It is postulated that the symmetric organization of plant lateral organs is based on two crossed axes, the abaxial-adaxial and the lateral axes. The PRESSED FLOWER (PRS) gene, the expression and function of which are dependent on the lateral axis, is reported in this study. In the prs mutant, growth of the lateral sep...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.931001

    authors: Matsumoto N,Okada K

    更新日期:2001-12-15 00:00:00

  • Ectodermal Wnt3/beta-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge.

    abstract::The formation of the apical ectodermal ridge (AER) is critical for the distal outgrowth and patterning of the vertebrate limb. Recent work in the chick has demonstrated that interplay between the Wnt and Fgf signaling pathways is essential in the limb mesenchyme and ectoderm in the establishment and perhaps the mainte...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1044903

    authors: Barrow JR,Thomas KR,Boussadia-Zahui O,Moore R,Kemler R,Capecchi MR,McMahon AP

    更新日期:2003-02-01 00:00:00

  • MYCN drives chemoresistance in small cell lung cancer while USP7 inhibition can restore chemosensitivity.

    abstract::Small cell lung cancer (SCLC) is an aggressive neuroendocrine cancer characterized by initial chemosensitivity followed by emergence of chemoresistant disease. To study roles for MYCN amplification in SCLC progression and chemoresistance, we developed a genetically engineered mouse model of MYCN-overexpressing SCLC. I...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.340133.120

    authors: Grunblatt E,Wu N,Zhang H,Liu X,Norton JP,Ohol Y,Leger P,Hiatt JB,Eastwood EC,Thomas R,Ibrahim AH,Jia D,Basom R,Eaton KD,Martins R,Houghton AM,MacPherson D

    更新日期:2020-09-01 00:00:00

  • The excess microsporocytes1 gene encodes a putative leucine-rich repeat receptor protein kinase that controls somatic and reproductive cell fates in the Arabidopsis anther.

    abstract::Cell differentiation is essential for the development of multicellular organisms. In flowering plants, the haploid male gametophytes (pollen grains) are generated in the anther from reproductive cells called microsporocytes. Several types of somatic cells ensure successful pollen development, and thus reproduction. Ho...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.997902

    authors: Zhao DZ,Wang GF,Speal B,Ma H

    更新日期:2002-08-01 00:00:00

  • p53 is essential for DNA methylation homeostasis in naïve embryonic stem cells, and its loss promotes clonal heterogeneity.

    abstract::DNA methylation is a key regulator of embryonic stem cell (ESC) biology, dynamically changing between naïve, primed, and differentiated states. The p53 tumor suppressor is a pivotal guardian of genomic stability, but its contributions to epigenetic regulation and stem cell biology are less explored. We report that, in...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.299198.117

    authors: Tovy A,Spiro A,McCarthy R,Shipony Z,Aylon Y,Allton K,Ainbinder E,Furth N,Tanay A,Barton M,Oren M

    更新日期:2017-05-15 00:00:00

  • Xenopus cdc7 function is dependent on licensing but not on XORC, XCdc6, or CDK activity and is required for XCdc45 loading.

    abstract::The assembly and disassembly of protein complexes at replication origins play a crucial role in the regulation of chromosomal DNA replication. The sequential binding of the origin recognition complex (ORC), Cdc6, and the minichromosome maintenance (MCM/P1) proteins produces a licensed replication origin. Before the in...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:

    authors: Jares P,Blow JJ

    更新日期:2000-06-15 00:00:00

  • Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila.

    abstract::Gut homeostasis is controlled by both immune and developmental mechanisms, and its disruption can lead to inflammatory disorders or cancerous lesions of the intestine. While the impact of bacteria on the mucosal immune system is beginning to be precisely understood, little is known about the effects of bacteria on gut...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1827009

    authors: Buchon N,Broderick NA,Chakrabarti S,Lemaitre B

    更新日期:2009-10-01 00:00:00

  • Not just scaffolding: plectin regulates actin dynamics in cultured cells.

    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

    doi:10.1101/gad.12.21.3442

    authors: Andrä K,Nikolic B,Stöcher M,Drenckhahn D,Wiche G

    更新日期:1998-11-01 00:00:00

  • MVH in piRNA processing and gene silencing of retrotransposons.

    abstract::VASA is an evolutionarily conserved RNA helicase essential for germ cell development. The mouse PIWI family proteins MILI and MIWI2 are involved in production of Piwi-interacting RNAs (piRNAs) in fetal male germ cells through a ping-pong amplification cycle. Expression of retrotransposons is elevated in MILI- and MIWI...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1902110

    authors: Kuramochi-Miyagawa S,Watanabe T,Gotoh K,Takamatsu K,Chuma S,Kojima-Kita K,Shiromoto Y,Asada N,Toyoda A,Fujiyama A,Totoki Y,Shibata T,Kimura T,Nakatsuji N,Noce T,Sasaki H,Nakano T

    更新日期:2010-05-01 00:00:00

  • In vivo analysis of the helix-turn-helix motif of the fushi tarazu homeo domain of Drosophila melanogaster.

    abstract::We report a systematic mutational analysis of the helix-turn-helix motif (HTH) of the fushi tarazu (ftz) homeo domain (HD) of Drosophila. We started out by testing the function of chimeric ftz proteins containing either a part of the Sex combs reduced (Scr) or the muscle segment homeobox (msh) HDs. By complementation ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.6.6.1082

    authors: Furukubo-Tokunaga K,Müller M,Affolter M,Pick L,Kloter U,Gehring WJ

    更新日期:1992-06-01 00:00:00

  • Deregulated matriptase causes ras-independent multistage carcinogenesis and promotes ras-mediated malignant transformation.

    abstract::Overexpression of the type II transmembrane serine protease matriptase is a highly consistent feature of human epithelial tumors. Here we show that matriptase possesses a strong oncogenic potential when unopposed by its endogenous inhibitor, HAI-1. Modest orthotopic overexpression of matriptase in the skin of transgen...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1300705

    authors: List K,Szabo R,Molinolo A,Sriuranpong V,Redeye V,Murdock T,Burke B,Nielsen BS,Gutkind JS,Bugge TH

    更新日期:2005-08-15 00:00:00

  • Loss of function of def selectively up-regulates Delta113p53 expression to arrest expansion growth of digestive organs in zebrafish.

    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...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1366405

    authors: Chen J,Ruan H,Ng SM,Gao C,Soo HM,Wu W,Zhang Z,Wen Z,Lane DP,Peng J

    更新日期:2005-12-01 00:00:00