Novel insight into KLF4 proteolytic regulation in estrogen receptor signaling and breast carcinogenesis.

ABSTRACT: Krüppel-like factor 4 (KLF4), a zinc finger-containing transcriptional factor, is a pivotal regulator of cellular fate. KLF4 has attracted considerable attention for its opposing effect in carcinogenesis as tumor suppressor (e.g. colorectal cancer) or oncoprotein (e.g. breast cancer), depending on tissue context, with the underlying mechanism remaining largely unknown. Here we report that KLF4 mediates estrogen signaling in breast cancer formation. Accumulation of KLF4 by inhibiting its turnover triggers estrogen-induced transactivation. We identified Von Hippel-Lindau, pVHL, as the protein that governs KLF4 turnover in breast cancer cells and demonstrated that estrogen-induced down-regulation of pVHL facilitates accumulation of KLF4. We provide mechanistic insights into KLF4 steady-state

SUBMITTER: Hu D 

PROVIDER: S-EPMC3340146 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature