Extracellular signal-regulated kinase 7, a regulator of hormone-dependent estrogen receptor destruction.

Henrich LM, Smith JA, Kitt D, Errington TM, Nguyen B, Traish AM, Lannigan DA
Mol Cell Biol. 2003 23 (17): 5979-88

PMID: 12917323 · PMCID: PMC180983 · DOI:10.1128/mcb.23.17.5979-5988.2003

Estrogen receptor alpha (ER alpha) degradation is regulated by ubiquitination, but the signaling pathways that modulate ER alpha turnover are unknown. We found that extracellular signal-regulated kinase 7 (ERK7) preferentially enhances the destruction of ER alpha but not the related androgen receptor. Loss of ERK7 was correlated with breast cancer progression, and all ER alpha-positive breast tumors had decreased ERK7 expression compared to that found in normal breast tissue. In human breast cells, a dominant-negative ERK7 mutant decreased the rate of endogenous ER alpha degradation >4-fold in the presence of hormone and potentiated estrogen responsiveness. ERK7 targets the ER alpha ligand-binding domain for destruction by enhancing its ubiquitination. Thus, ERK7 is a novel regulator of estrogen responsiveness through its control of ER alpha turnover.

MeSH Terms (23)

Animals Binding Sites Breast Breast Neoplasms Cells, Cultured Cricetinae Cysteine Proteinase Inhibitors Estrogen Receptor alpha Extracellular Signal-Regulated MAP Kinases Female Hormones Humans Kidney Leupeptins Mitogen-Activated Protein Kinases Mutation Peptide Hydrolases Phosphorylation Proteasome Endopeptidase Complex Receptors, Estrogen Reference Values Signal Transduction Ubiquitin

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