Mechanisms of regulation of G11α protein by dexamethasone in osteoblastic UMR 106–01 cells

Abstract

We have previously demonstrated that glucocorticoids increased Gq/11α protein expression and phospholipase C activity in the rat osteosarcoma cell line UMR 106–01. In this study, we demonstrated that G11α is the primary Gq-subtype family member expressed in UMR cells. Dexamethasone treatment increased the expression of G11α protein in both a time- and a dose-dependent manner. Glucocorticoid treatment significantly increased the half-life of G11α protein from 20.3 to 63 h. Steady-state G11α mRNA level was also increased by glucocorticoid treatment by ∼70%. This change was not the result of changes in RNA stability but rather the result of increased transcription, because the glucocorticoid-mediated upregulation of G11α mRNA was blocked by the transcription inhibitor actinomycin D. The dexamethasone induction of G11α mRNA occurred after a time lag of 12–24 h and was blocked by the protein synthesis inhibitor cycloheximide. These results suggest that the dexamethasone-induced rise in G11α protein results primarily from changes in the degradation rate of the protein, whereas changes in G11α mRNA play a smaller role and require de novo synthesis of regulatory protein(s).