TY - JOUR
T1 - Valproic acid causes proteasomal degradation of DICER and influences miRNA expression
AU - Zhang, Zhaiyi
AU - Convertini, Paolo
AU - Shen, Manli
AU - Xu, Xiu
AU - Lemoine, Frédéric
AU - De La Grange, Pierre
AU - Andres, Douglas A.
AU - Stamm, Stefan
PY - 2013/12/17
Y1 - 2013/12/17
N2 - Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar disorders. Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA's clinical features. We found that VPA induces the proteasomal degradation of DICER, a key protein in the generation of micro RNAs. Unexpectedly, the concentration of several micro RNAs increases after VPA treatment, which is caused by the upregulation of their hosting genes prior to DICER degradation. The data suggest that a loss of DICER protein and changes in micro RNA concentration contributes to the clinical properties of VPA. VPA can be used experimentally to down regulate DICER protein levels, which likely reflects a natural regulation of DICER.
AB - Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar disorders. Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA's clinical features. We found that VPA induces the proteasomal degradation of DICER, a key protein in the generation of micro RNAs. Unexpectedly, the concentration of several micro RNAs increases after VPA treatment, which is caused by the upregulation of their hosting genes prior to DICER degradation. The data suggest that a loss of DICER protein and changes in micro RNA concentration contributes to the clinical properties of VPA. VPA can be used experimentally to down regulate DICER protein levels, which likely reflects a natural regulation of DICER.
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U2 - 10.1371/journal.pone.0082895
DO - 10.1371/journal.pone.0082895
M3 - Article
C2 - 24358235
AN - SCOPUS:84892906480
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e82895
ER -