title: KIAA0368-deficiency affects disassembly of 26S proteasome under oxidative stress condition.
abstract: Many cellular stresses cause damages of intracellular proteins, which are eventually degraded by the ubiquitin and proteasome system. The proteasome is a multicatalytic protease complex composed of 20S core particle and the proteasome activators that regulate the proteasome activity. Extracellular mutants 29 (Ecm29) is a 200 kDa protein encoded by KIAA0368 gene, associates with the proteasome, but its role is largely unknown. Here, we generated KIAA0368-deficient mice and investigated the function of Ecm29 in stress response. KIAA0368-deficient mice showed normal peptidase activity and proteasome formation at normal condition. Under stressed condition, 26S proteasome dissociates in wild-type cells, but not in KIAA0368(-/-) cells. This response was correlated with efficient degradation of damaged proteins and resistance to oxidative stress of KIAA0368(-/-) cells. Thus, Ecm29 is involved in the dissociation process of 26S proteasome, providing clue to analyse the mechanism of proteasomal degradation under various stress condition.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Haratake
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Sato
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Tsuruta
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan tchiba@biol.tsukuba.ac.jp.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease
keywords: oxidative stress; proteasome; proteasome activators; protein degradation; ubiquitin