2008
DOI: 10.1152/ajprenal.90420.2008
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Acceleration of polycystic kidney disease progression in cpk mice carrying a deletion in the homeodomain protein Cux1

Abstract: Polycystic kidney diseases (PKD) are inherited as autosomal dominant (ADPKD) or autosomal recessive (ARPKD) traits and are characterized by progressive enlargement of renal cysts. Aberrant cell proliferation is a key feature in the progression of PKD. Cux1 is a homeobox gene that is related to Drosophila cut and is the murine homolog of human CDP (CCAAT Displacement Protein). Cux1 represses the cyclin kinase inhibitors p21 and p27, and transgenic mice ectopically expressing Cux1 develop renal hyperplasia. Howe… Show more

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Cited by 29 publications
(47 citation statements)
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“…Cux1 is a homeobox gene that represses the cyclin kinase inhibitors p21 and p27, and transgenic mice ectopically expressing Cux1 develop renal hyperplasia (107). A 246-amino acid deletion in Cux1 accelerates PKD progression in the cpk model of ARPKD (11), and the ensuing phenotype was explained by a missing cathepsin L cleavage site in the truncated Cux1 mutant, which thereby maintains increased tubular cell proliferation and apoptosis. Cux1 is proteolytically processed by a nuclear isoform of cathepsin L (10).…”
Section: Figurementioning
confidence: 99%
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“…Cux1 is a homeobox gene that represses the cyclin kinase inhibitors p21 and p27, and transgenic mice ectopically expressing Cux1 develop renal hyperplasia (107). A 246-amino acid deletion in Cux1 accelerates PKD progression in the cpk model of ARPKD (11), and the ensuing phenotype was explained by a missing cathepsin L cleavage site in the truncated Cux1 mutant, which thereby maintains increased tubular cell proliferation and apoptosis. Cux1 is proteolytically processed by a nuclear isoform of cathepsin L (10).…”
Section: Figurementioning
confidence: 99%
“…In both human ADPKD cells and in kidneys of mice with a targeted deletion in Pkd1, a murine model of PKD, decreased nuclear cathepsin L levels are associated with increased levels of Cux1 protein in the cystic cells in vitro and the cysts in vivo (11). These results suggest a mechanism by which reduced Cux1 processing by nuclear cathepsin L results in the accumulation of Cux1, downregulation of p21/p27, and increased cell proliferation in PKD (11). Furthermore, they provide proof of principle of the hypothesis that nuclear cathepsin L is capable of processing transcription factors that control important cellular programs, such as growth.…”
Section: Figurementioning
confidence: 99%
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“…Importantly, several mouse models of polycystic kidney disease generated by mutating ciliogenic genes show downregulation of p27 Kip1 (Alcalay et al, 2008;Cadieux et al, 2008). Thus, it will be interesting to determine whether dysregulation of cell cycle via p27…”
Section: Kip2mentioning
confidence: 99%
“…Moreover, a shift in activity from cathepsin L to D and E was detected. Reduced proteolytic processing of Cux1 by decreased cathepsin L activity is thought to contribute to cyst growth in murine Pkd1 −/− cells (Alcalay et al 2008). Cux1, the murine homolog of human CDP, is a homeobox gene that represses the cyclin kinase inhibitors p21 and p27.…”
Section: Adpkd Biomarkersmentioning
confidence: 99%