Negative regulatory role of annexin-A1 in 14-3-3eta-mediated glucocorticoid receptor transcriptional activation.
Annexin-A1 (ANX-1) is involved in glucocorticoid receptor (GR)-mediated signal transduction. However, the molecular mechanism by which ANX-1 plays a role in GR signaling is not fully understood. Recently, we reported that 14-3-3eta inhibits degradation of GR, resulting in an increase in GR transcriptional activity. In this study, we have addressed the role of ANX-1 in 14-3-3eta-induced enhancement of GR transactivation. ANX-1 abolished the increase in GR transcriptional activity due to 14-3-3eta. ANX-1 had no effect on the protein level of GR. However, ANX-1 abrogated the inhibitory effect of 14-3-3eta on GR degradation, which causes a decrease in GR stability in the nucleus. Our results indicate that ANX-1 functions as a negative regulator of GR transcriptional activation by inhibiting 14-3-3eta-induced up-regulation of GR.
Sung
Ho Joong
HJ
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Ryang
Yong Suk
YS
Kim
Yoon Suk
YS
Jang
Sung-Wuk
SW
Na
Doe Sun
DS
Ko
Jesang
J
D048948:14-3-3 Proteins / Q000494:pharmacology*; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D003907:Dexamethasone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*
D048948:14-3-3 Proteins; D017305:Annexin A1; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone