TY - JOUR
T1 - RhoA Controls Retinoid Signaling by ROCK Dependent Regulation of Retinol Metabolism
AU - García-Mariscal, Alberto
AU - Peyrollier, Karine
AU - Basse, Astrid
AU - Pedersen, Esben Ditlev Kølle
AU - Rühl, Ralph
AU - van Hengel, Jolanda
AU - Brakebusch, Cord
PY - 2018/9/3
Y1 - 2018/9/3
N2 - The ubiquitously expressed small GTPase RhoA is essential for embryonic development and mutated in different cancers. Functionally, it is well described as a regulator of the actin cytoskeleton, but its role in gene regulation is less understood. Using primary mouse keratinocytes with a deletion of the RhoA gene, we have now been exploring how the loss of RhoA affects gene expression. Performing transcription factor reporter assays, we found a significantly decreased activity of a RAR luciferase reporter in RhoA-null keratinocytes. Inhibition of the RhoA effector ROCK in control cells reproduced this phenotype. ATRA and retinal, but not retinol increased RAR reporter activity of keratinocytes with impaired RhoA/ROCK signaling, suggesting that retinol metabolism is regulated by RhoA/ROCK signaling. Furthermore a significant percentage of known ATRA target genes displayed altered expression in RhoA-null keratinocytes. These data reveal an unexpected link between the cytoskeletal regulator RhoA and retinoid signaling and uncover a novel pathway by which RhoA regulates gene expression.
AB - The ubiquitously expressed small GTPase RhoA is essential for embryonic development and mutated in different cancers. Functionally, it is well described as a regulator of the actin cytoskeleton, but its role in gene regulation is less understood. Using primary mouse keratinocytes with a deletion of the RhoA gene, we have now been exploring how the loss of RhoA affects gene expression. Performing transcription factor reporter assays, we found a significantly decreased activity of a RAR luciferase reporter in RhoA-null keratinocytes. Inhibition of the RhoA effector ROCK in control cells reproduced this phenotype. ATRA and retinal, but not retinol increased RAR reporter activity of keratinocytes with impaired RhoA/ROCK signaling, suggesting that retinol metabolism is regulated by RhoA/ROCK signaling. Furthermore a significant percentage of known ATRA target genes displayed altered expression in RhoA-null keratinocytes. These data reveal an unexpected link between the cytoskeletal regulator RhoA and retinoid signaling and uncover a novel pathway by which RhoA regulates gene expression.
U2 - 10.1080/21541248.2016.1248272
DO - 10.1080/21541248.2016.1248272
M3 - Journal article
C2 - 27754752
SN - 2154-1248
VL - 9
SP - 433
EP - 444
JO - Small GTPases
JF - Small GTPases
IS - 5
ER -
