The E3 Ligase CHIP Mediates Ubiquitination and Degradation of Mixed Lineage Kinase 3 and Mixed Lineage Kinase 4 Beta
Year: 2015
Type: article
Abstract: and osmotic shock-induced activation of ERK, p38, and JNK.We assessed the role of CHIP in modulating MLK3 and MLK4β protein levels.GA, thermostress, and osmotic shock-induced degradation of MLK3 is abolished in cells with CHIP siRNA knockdown.CHIP overexpression promotes ubiquitination and a proteasome-dependent reduction of MLK3.CHIP interacts with both MLK3 and MLK4β proteins in vitro and with MLK3 in cells; and CHIP ubiquitinates MLK3 and MLK4β (with UbcH5 E2s) in vitro.Furthermore, CHIP-dependent regulation of MLK3 is required for invasion of SKOV3 cells.These findings suggest that CHIP regulates MLK3 and MLK4β protein levels and, in part, cell invasiveness by facilitating ubiquitination and proteasome-dependent degradation of MLK3.I would like to dedicate this work to my eccentric and loving family: my amazing mom, Irina Blessing, my wonderful dad, John Blessing, my sweet grandmother, Klaudia Alekseyenko, and my whimsical grandfather, Nikolai Alekseyenko.Their support, encouragement and love have gotten me through my toughest times in graduate school
Author: Natalya A. Blessing
Institution: University of Toledo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2524023190