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Title: 1alpha,25-dihydroxyvitamin D(3)-induced down-regulation of the checkpoint proteins. Chk1 and Claspin, is mediated by the pocket proteins
Authors: Verlinden, Lieve
Eelen, Guy
Van Hellemont, Ruth
Engelen, Kristof
Beullens, Ine
Van Camp, Mark
Marchal, Kathleen
Mathieu, Chantal
Bouillon, Roger
Verstuyf, Annemieke # ×
Issue Date: Mar-2007
Publisher: Pergamon Press
Series Title: Journal of Steroid Biochemistry and Molecular Biology vol:103 issue:3-5 pages:411-415
Abstract: A previous cDNA microarray analysis in murine MC3T3-E1 osteoblasts revealed a cluster of genes involved in cell cycle progression that was significantly down-regulated after a single treatment with 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] [L. Verlinden, G. Eelen, I. Beullens, M. Van Camp, P. Van Hummelen, K. Engelen, R. Van Hellemont, K. Marchal, B. De Moor, F. Foijer, H. Te Riele, M. Beullens, M. Bollen, C. Mathieu, R. Bouillon, A. Verstuyf, Characterization of the condensin component Cnap1 and protein kinase Melk as novel E2F target genes down-regulated by 1,25-dihydroxyvitamin D3, J. Biol. Chem. 280 (45) (2005) 37319-37330]. Among those genes were the DNA replication and DNA damage checkpoint proteins, Chk1 and Claspin, of which the human homologues were recently shown to be E2F-responsive. Quantitative real-time PCR experiments in 1,25(OH)(2)D(3)-treated MC3T3-E1 cells confirmed the down-regulation observed in the microarray experiment. Moreover, Chk1 and Claspin promoter activities were also reduced after incubation with 1,25(OH)(2)D(3), and this reduction was mediated through the E2F recognition motifs within their promoters because mutation of these motifs almost completely abolished the repressive effect of 1,25(OH)(2)D(3). The antiproliferative effect of 1,25(OH)(2)D(3) as well as its potential to down-regulate the expression of Chk1 and Claspin depended on the pocket proteins p107 and p130 because 1,25(OH)(2)D(3) lost its antiproliferative action and failed to repress these E2F-target genes in p107(-/-);p130(-/-)-cells, but not in pRb(-/-)-cells.
ISSN: 0960-0760
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Centre of Microbial and Plant Genetics
Division of Mechatronics, Biostatistics and Sensors (MeBioS)
ESAT - ELECTA, Electrical Energy Computer Architectures
Medical Clerkships Centers
ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
× corresponding author
# (joint) last author

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