Title: Characterization of the condensin component Cnap1 and protein kinase Melk as novel E2F target genes
Authors: Verlinden, Lieve
Eelen, Guy
Beullens, Ine
Van Camp, Mark
Van Hummelen, Paul
Engelen, Kristof
Van Hellemont, Ruth
Marchal, Kathleen
De Moor, Bart
Foijer, Floris
Te Riele, Hein
Beullens, Monique
Bollen, Mathieu
Mathieu, Chantal
Bouillon, Roger
Verstuyf, Annemieke # ×
Issue Date: Nov-2005
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:280 issue:45 pages:37319-37330
Abstract: 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) has potent antiproliferative effects characterized by a hampered G(1)/S transition. cDNA microarrays were used to monitor expression of 21,492 genes in MC3T3-E1 mouse osteoblasts at 1, 6, 12, 24, and 36 h after treatment with 1,25(OH)(2)D(3). Statistical analysis revealed a cluster of genes that were strongly down-regulated by 1,25(OH)(2)D(3) and which not only function in cell cycle regulation and DNA replication but also mediate checkpoint control, DNA repair, chromosome modifications, and mitosis. Because many of these genes were shown earlier to be regulated by the transcriptional repressor E2F4, the intergenic regions of these 1,25(OH)(2)D(3)-down-regulated genes were searched for the presence of E2F binding sites. This led to the characterization of two novel E2F target genes, chromosome condensation-related SMC-associated protein 1 (Cnap1) and maternal embryonic leucine zipper kinase (Melk). Transfection studies and site-directed mutagenesis confirmed Cnap1 and Melk to be bona fide E2F targets. Repression of Cnap1 and Melk by 1,25(OH)(2)D(3) was confirmed not only in MC3T3-E1 cells but also in several other bone-unrelated cell types. This down-regulation as well as the antiproliferative effect of 1,25(OH)(2)D(3) depended on the pocket proteins p107 and p130 because 1,25(OH)(2)D(3) failed to repress these E2F target genes and lost its antiproliferative action in p107(-/-);p130(-/-) cells but not in pRb(-/-) cells.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Centre of Microbial and Plant Genetics
ESAT - ELECTA, Electrical Energy Computer Architectures
Biochemistry Section (Medicine) (-)
ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
Laboratory of Biosignaling & Therapeutics
× corresponding author
# (joint) last author

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