RhoA Controls Retinoid Signaling by ROCK Dependent Regulation of Retinol Metabolism
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RhoA Controls Retinoid Signaling by ROCK Dependent Regulation of Retinol Metabolism. / García-Mariscal, Alberto; Peyrollier, Karine; Basse, Astrid; Pedersen, Esben Ditlev Kølle; Rühl, Ralph; van Hengel, Jolanda; Brakebusch, Cord.
In: Small GTPases, Vol. 9, No. 5, 2018, p. 433–444.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2018
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 signalling, suggesting that retinol metabolism is regulated by RhoA/ROCK signalling. 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 signalling 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 signalling, suggesting that retinol metabolism is regulated by RhoA/ROCK signalling. 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 signalling 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
VL - 9
SP - 433
EP - 444
JO - Small GTPases
JF - Small GTPases
SN - 2154-1248
IS - 5
ER -
ID: 167584482