Differential expression of Cux-1 and p21 in polycystic kidneys from Pkd1 null and cpk mice

Sharma, Madhulika; Brantley, Jennifer G.; Alcalay, Neal I.; Zhou, Jing; Heystek, Engela; Maser, Robin L.; Heuvel, Gregory B. Vanden

doi:10.1111/j.1523-1755.2005.67099.x

Cited by 17 publications

(42 citation statements)

References 34 publications

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“…Cux1 has previously been implicated in renal cyst formation as its expression was shown to be elevated in both Pkd1 Ϫ/Ϫ and cpk mouse models of polycystic kidney disease (40,41). However, which Cux1 isoform(s) was overexpressed could not be assessed through immunohistochemical assays because there are no antibodies that specifically recognize the short isoforms without detecting the full-length protein.…”

Section: Discussionmentioning

confidence: 99%

“…Null Mice-Overexpression of the full-length Cux1 in Pkd1 Ϫ/Ϫ polycystic kidneys was reported previously (41). To determine whether p75, a more transcriptionally active isoform of Cux1 was also expressed in Pkd1 Ϫ/Ϫ kidneys, a cRNA probe was designed to recognize the p75-Cux1-specific region within intron 20 (38).…”

Section: Expression Of Cux1 Isoform P75 Is Increased In the Kidneys Omentioning

confidence: 99%

“…Cux1 overexpression is detected in polycystic kidneys of the congenital polycystic (cpk) (40) and Pkd1 null mouse models (41). The precise activity of Cux1 in these models remains unclear as Cux1 overexpression is associated with increased proliferation in the Pkd1 model and increased apoptosis in the cpk model (41).…”

mentioning

confidence: 99%

“…The precise activity of Cux1 in these models remains unclear as Cux1 overexpression is associated with increased proliferation in the Pkd1 model and increased apoptosis in the cpk model (41). In addition, transgenic mice expressing the CUX1 p200 isoform under the control of the CMV enhancer/ promoter displayed multiorgan (including renal) hyperplasia associated with glomerular abnormalities, interstitial fibrosis, and proteinuria (42,43).…”

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confidence: 99%

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Polycystic Kidneys Caused by Sustained Expression of Cux1 Isoform p75

Cadieux

Harada

Paquet

et al. 2008

Journal of Biological Chemistry

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The transcriptional regulator Cux1 (CDP, Cutl1) is aberrantly expressed in mouse models for polycystic kidney disease. Here we show that p75-Cux1, the shortest isoform of Cux1, transcribed from an alternative promoter within intron 20, is also deregulated in polycystic kidneys derived from Pkd1 mutant embryos. To determine the role of the p75-Cux1 isoform in cystogenesis, we generated transgenic mice expressing p75-CUX1 in the kidneys and other tissues. Strikingly, these animals developed polycystic kidneys at variable penetrance and severity, correlating with transgene expression levels. Histological and marker analysis of p75-CUX1-derived polycystic kidneys revealed renal cysts derived from the tubular nephron, supporting a model of autosomal dominant polycystic kidney disease. Transgenic p75-CUX1 kidneys additionally showed an up-regulation of the protooncogene c-myc and a down-regulation of the cyclin-dependent kinase inhibitor p27. Chromatin affinity purification experiments confirmed the direct interaction of Cux1 with the c-myc and p27 promoters. These molecular alterations were accompanied by an increase in cilia length and in the proliferative index of epithelial cells lining the cysts. Together, these results identify an important role for the short isoform of CUX1 in polycystic kidney disease development.

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Section: Discussionmentioning

confidence: 99%

Section: Expression Of Cux1 Isoform P75 Is Increased In the Kidneys Omentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Polycystic Kidneys Caused by Sustained Expression of Cux1 Isoform p75

Cadieux

Harada

Paquet

et al. 2008

Journal of Biological Chemistry

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“…It is not possible to evaluate the experimental evidence, as the gene list was not provided. Certainly, the idea that CUX1 represses genes that are involved in cell cycle progression runs contrary to the bulk of the evidence showing that CUX1 stimulates expression of histone genes and many genes involved in DNA replication, while repressing expression of the cyclin-dependent kinase inhibitors p21 and p27 (REFS 15,41,60,62,(68)(69)(70)(71)(72)(73)(74)(75). Moreover, in cell-based assays, MEFs from Cux1-knockout mice showed a longer G1 phase and proliferated more slowly than their wild-type counterparts; whereas, in many cell types, ectopic expression of p110 CUX1 accelerated S phase entry and stimulated proliferation 21,22 .…”

Section: Functions Of Cux1 That Suppress Tumour Developmentmentioning

confidence: 99%

CUX1, a haploinsufficient tumour suppressor gene overexpressed in advanced cancers

2014

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Cux‐1 and Cux‐2 control the development of Reelin expressing cortical interneurons

Cubelos

Sebastián-Serrano

Kim

et al. 2008

Developmental Neurobiology

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Homeodomain transcription factors play important roles in the specification and differentiation of neuronal subpopulations. In the cerebral cortex, the expression patterns of Cux-1 and Cux-2 in the medial ganglionic eminence (MGE) suggest a role for these transcription factors in the development of interneurons, a heterogeneous neuronal population. In this report, we describe expression of Cux-1 and Cux-2 proteins in Reelin-secreting interneurons of the cortical plate, but not in calretinin or parvalbumin subpopulations. The role of Cux genes in the development of Reelin positive neurons was studied using Cux-1 and Cux-2 knockout mice. These experiments demonstrate that Cux-1À/À; Cux-2À/À double mutation is embryonically lethal. Although this phenotype is highly penetrant, a small proportion of mice develop to birth (P0).Analysis of these animals demonstrate that expression of Reelin is completely absent in layers II-IV of Cux-1À/À; Cux-2À/À double mutant mice, but it is not affected in the cortex of Cux-1À/À or Cux-2À/À single mutants. No Cux-1À/À; Cux-2À/À double-mutant were collected after P0. Since, GABA-ergic populations mature at late postnatal stages, this did not allow us to analyze the expression of subclass specific markers and define the affected interneuron subpopulations. Our analysis of Cux-1À/À; Cux-2À/À double mutant thus demonstrates essential yet redundant roles for Cux-1 and Cux-2 in specifying Reelin expressing cortical interneurons. ' 2008 Wiley Periodicals, Inc. Develop Neurobiol 68: 917-925, 2008

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Differential expression of Cux-1 and p21 in polycystic kidneys from Pkd1 null and cpk mice

Cited by 17 publications

References 34 publications

Polycystic Kidneys Caused by Sustained Expression of Cux1 Isoform p75

Polycystic Kidneys Caused by Sustained Expression of Cux1 Isoform p75

CUX1, a haploinsufficient tumour suppressor gene overexpressed in advanced cancers

Cux‐1 and Cux‐2 control the development of Reelin expressing cortical interneurons

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