20 Feb 2009 Our last article "Antiproliferative effect of ascorbic acid is associated with the inhibition of genes necessary to cell cycle progression."PLoS ONE. 2009;4(2) has been selected for Faculty of 1000 Biology.
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Recently, using an animal model of Charcot-Marie-Tooth human disorder,
we showed that ascorbic acid (AA) represses PMP22 gene expression by
acting on intracellular cAMP concentrations. In this work, we present
kinetics data on the inhibitory effect of AA upon adenylate cyclase
activity. The data show that this molecule acts as a competitive
inhibitor of the enzyme, a finding that opens new pharmacological
avenues.
Polycystin-2 (PC-2), a protein encoded by PKD2 and involved in
autosomal dominant polycystic kidney disease (ADPKD), is a
non-selective cationic channel recently implicated in the function of
primary cilia. We recently constructed a new animal model in the form
of a transgenic mouse with a BAC-containing human PKD2 inserted in its
genome. Two transgenic mouse lines overexpressing human PKD2 showed
mitotic instability. Fibroblasts from these transgenic mouse lines have
abnormal chromosomal numbers. These lines also have supernumerary
centrosomes. PC-2 overexpression is associated with mitotic instability
and centrosome overduplication. PC-2 therefore seems to play a role in
centrosome duplication, and this hypothesis is being evaluated in other
models.
