BRMS1 Suppresses Lung Cancer Metastases through an E3 Ligase Function on Histone Acetyltransferase p300
Year: 2012
Type: article
Abstract: The mechanisms through which the metastasis suppressor gene BRMS1 functions are poorly understood. Herein, we report the identification of a previously undescribed E3 ligase function of BRMS1 on the histone acetyltransferase p300. BRMS1 induces polyubiquitination of p300, resulting in its proteasome-mediated degradation. We identify BRMS1 as the first eukaryote structural mimic of the bacterial IpaH E3 ligase family and establish that the evolutionarily conserved CXD motif located in BRMS1 is responsible for its E3 ligase function. Mutation of this E3 ligase motif not only abolishes BRMS1-induced p300 polyubiquitination and degradation, but importantly, dramatically reduces the metastasis suppressor function of BRMS1 in both in vitro and in vivo models of lung cancer metastasis.
Source: Cancer Research
Institution: University of Virginia
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: National Cancer Institute
Awards: Role of IKK in NSCLC: Modulation of SMRT and NF-kappaB, Epigenetic and post-translational regulation of the metastasis suppressor BRMS1, Inflammatory Cytokines Link NF-kappaB with Bim Degradation and Metastasis, Cancer Research Training Program: From Molecular Mechanisms to Therapeutic Strategies, University of Virginia Cancer Center Support Grant
OpenAlex ID: W2050857920