ISSN:
1524-475X
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Ability of keratinocytes to migrate relays on appropriate citoskeletal network and is one of the key prerequisites of wound healing. Keratins K6 and K16 are the cytoskeletal components that mark migrating keratinocytes. We found K6/K16 to be differentially regulated in microarray experiments: induced in the wound healing and suppressed by inhibitors of wound healing, glucocorticoids (GC). We have shown previously that GC suppress K6/K16 expression through a unique molecular mechanism that involves four monomers of glucocorticoid receptor (GR). Because β-catenin interacts with members of the nuclear receptor family, such as retinoic acid receptors (RAR) and androgen receptor (AR) and participates in both activation and repression of transcription and similarly to GC inhibits keratinocytes migration we hypothesized that β-catenin participates in GC-mediated repression of K6/K16. To test if β-catenin participates in K6/K16 suppression by GC we used co-transfection experiments, with primary human keratinocytes. By itself, β-catenin did not affect K6/K16 expression. However, in the presence of GC, β-catenin acted as a GR co-repressor further suppressing K6/K16 expression. Moreover, protein arginine methyltransferase CARM-1 enhances this co-repression, suggesting that the complex that suppresses K6/K16 promoters contains GR, β-catenin and CARM-1. Similarly, β-catenin functioned as a co-repressor of GR even if we just incubated keratinocytes with LiCl (stabilized β-catenin) rather than transfected its expression plasmid. It has been shown that β-catenin and CARM-1 bind each other in a co-activator complex with AR, but it was not known if this complex has a co-repressing capacity. We have shown that by participating in the GC-mdiated repression of K6/K16 transcription as a co-repressor with CARM1, β-catenin contributes to the inhibition of keratinocyte migration through altering the cytoskeletal network and subsequent inhibition of wound healing.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1067-1927.2004.0abstractek.x
Permalink
