MAPK Targets Progesterone Receptors for Degradation

Science's STKE  15 Feb 2000:
Vol. 2000, Issue 19, pp. tw9
DOI: 10.1126/stke.2000.19.tw9

Progesterone receptors are down-regulated in response to ligand binding. Lange et al. demonstrated that one mechanism of down-regulation of progesterone receptors was phosphorylation by mitogen-activated protein kinase (MAPK) leading to ubiquitination and destruction by the 26S proteasome. Inhibitors of the 26S proteasome or p44 and p42 MAP kinases stabilized progesterone A and B receptors in breast cancer cells. Furthermore, mutation of one of the MAPK consensus phosphorylation sites on the progesterone receptors stabilized both ligand bound and free receptors. Immature progesterone receptors were also degraded by the 26S proteasome; however, degradation was independent of MAPK phosphorylation.

Lange, C.A., Shen, T., and Horwitz, K.B. (2000) Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome. Proc. Natl. Acad. Sci. 97: 1032-1037. [Abstract] [Full Text]