Editors' ChoiceTranscriptional Inhibition

RXRα Stressed Out by MKK4

STKE  17 Oct 2000:
Vol. 2000, Issue 54, pp. tw3
DOI: 10.1126/stke.2000.54.tw3

Stressful stimuli inhibit the activation of retinoids, but the mechanism of this inhibition has remained a mystery. Now Lee et al. have uncovered some of the molecular steps required for retinoid inhibition. Cells treated with anisomycin or expressing the constitutively activated stress-associated protein kinase kinase SEK1 (MKK4) showed reduced retinoic acid (RA)-mediated gene expression. Similarly treated cells contained phosphorylated retinoic X receptor (RXR) α but not phospho-RARα. MKK4 and JNK1 (Jun NH2-terminal kinase 1), the kinase downstream of MKK4 both phosphorylated RXRα, however, only phosphorylation of RXRα on Tyr249 by MKK4 was essential for inhibiting RA-mediated transcription. Anisomycin-induced phosphorylation of RXRα was decreased in cells lacking MKK4. Thus, MKK4-directed RXRα phosphorylation may be important for attenuating RA responses in the presence of stress.

Lee, H.-Y., Suh, Y.-A., Robinson, M.J., Clifford, J.L., Hong, W.K., Woodgett, J.R., Cobb, M.H., Mangelsdorf, D.J., and Kurie, J.M. (2000) Stress pathway activation induces phosphorylation of retinoid X receptor. J. Biol. Chem. 275: 32193-32199. [Abstract] [Full Text]