Phosphorylation of ICBP90 by protein kinase A enhances topoisomerase IIalpha expression.
Inverted CCAAT box binding protein of 90kDa (ICBP90) is a nuclear protein involved in the topoisomerase IIalpha (TopoIIalpha) gene expression. It belongs to a family of E3 ligases of the RING finger type and its expression is deregulated in cancer cells. Previous studies have shown that high expression of ICBP90 may impair the control of G1/S transition of the cell cycle in various cancer cell lines. Since PKA signaling pathway is involved in G1/S transition of the cell cycle, the aim of the present study was to investigate whether cAMP signaling pathways involve phosphorylation of ICBP90. Here, we show that phosphorylation of ICBP90 through the cAMP signaling pathway accelerates exit of forskolin-treated cells from the G1 phase and increases binding of ICBP90 to the ICB2 element of the TopoIIalpha gene promoter with a subsequent increase of TopoIIalpha expression. We identify S298 of ICBP90 as target for PKA. We propose that cAMP signaling pathway enhances TopoIIalpha expression through ICBP90 phosphorylation, which may be one of the major events involved in the G1/S transition.
Trotzier
Marie-Aline
MA
Institut National de la Santé et de la Recherche Médicale, Inserm UMR-S 392, Faculté de Pharmacie, 74 route du Rhin, B.P. 60024, 67401 Illkirch Cedex, France.
Bronner
Christian
C
Bathami
Kawtar
K
Mathieu
Eric
E
Abbady
Abdul-Qader
AQ
Jeanblanc
Michaël
M
Muller
Christian D
CD
Rochette-Egly
Cécile
C
Mousli
Marc
M
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019556:COS Cells; D005576:Colforsin / Q000494:pharmacology; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D024202:Electrophoretic Mobility Shift Assay; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012694:Serine / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
D000951:Antigens, Neoplasm; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005576:Colforsin; D012694:Serine; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D004250:DNA Topoisomerases, Type II