Open AccessExtracellular Signal-Regulated Kinase 7, a Regulator of Hormone-Dependent Estrogen Receptor Destruction
Author(s) -
Lorin M. Henrich,
Jeffrey A. Smith,
Danielle Kitt,
Tim Errington,
Binh Nguyen,
Abdulmaged M. Traish,
Deborah A. Lannigan
Publication year - 2003
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.23.17.5979-5988.2003
Subject(s) - biology , estrogen receptor , regulator , estrogen , estrogen receptor beta , estrogen receptor alpha , endocrinology , extracellular , signal transduction , medicine , cancer research , microbiology and biotechnology , receptor , kinase , ubiquitin , breast cancer , cancer , biochemistry , genetics , gene
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.