Mechanisms of regulation of G11a protein by dexamethasone in osteoblastic UMR 106–01 cells

Cheung, Ricky, and Jane Mitchell. Mechanisms of regulation of G11a protein by dexamethasone in osteoblastic UMR 106–01 cells. Am J Physiol Endocrinol Metab 282: E24–E30, 2002.—We have previously demonstrated that glucocorticoids increased Gq/11a protein expression and phospholipase C activity in the rat osteosarcoma cell line UMR 106–01. In this study, we demonstrated that G11a is the primary Gq-subtype family member expressed in UMR cells. Dexamethasone treatment increased the expression of G11a protein in both a timeand a dose-dependent manner. Glucocorticoid treatment significantly increased the half-life of G11a protein from 20.3 to 63 h. Steady-state G11a 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 G11a mRNA was blocked by the transcription inhibitor actinomycin D. The dexamethasone induction of G11a 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 G11a protein results primarily from changes in the degradation rate of the protein, whereas changes in G11a mRNA play a smaller role and require de novo synthesis of regulatory protein(s).