title: Redox regulation of the proteasome via S-glutathionylation.
abstract: The proteasome is a multimeric and multicatalytic intracellular protease responsible for the degradation of proteins involved in cell cycle control, various signaling processes, antigen presentation, and control of protein synthesis. The central catalytic complex of the proteasome is called the 20S core particle. The majority of these are flanked on one or both sides by regulatory units. Most common among these units is the 19S regulatory unit. When coupled to the 19S unit, the complex is termed the asymmetric or symmetric 26S proteasome depending on whether one or both sides are coupled to the 19S unit, respectively. The 26S proteasome recognizes poly-ubiquitinylated substrates targeted for proteolysis. Targeted proteins interact with the 19S unit where they are deubiquitinylated, unfolded, and translocated to the 20S catalytic chamber for degradation. The 26S proteasome is responsible for the degradation of major proteins involved in the regulation of the cellular cycle, antigen presentation and control of protein synthesis. Alternatively, the proteasome is also active when dissociated from regulatory units. This free pool of 20S proteasome is described in yeast to mammalian cells. The free 20S proteasome degrades proteins by a process independent of poly-ubiquitinylation and ATP consumption. Oxidatively modified proteins and other substrates are degraded in this manner. The 20S proteasome comprises two central heptamers (β-rings) where the catalytic sites are located and two external heptamers (α-rings) that are responsible for proteasomal gating. Because the 20S proteasome lacks regulatory units, it is unclear what mechanisms regulate the gating of α-rings between open and closed forms. In the present review, we discuss 20S proteasomal gating modulation through a redox mechanism, namely, S-glutathionylation of cysteine residues located in the α-rings, and the consequence of this post-translational modification on 20S proteasomal function.
authors.affiliation: Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Marilene
authors.initials: M
authors.lastname: Demasi
authors.affiliation: Departamento de Genética e Biologia Evolutiva, IB-Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Luis E S
authors.initials: LE
authors.lastname: Netto
authors.affiliation: Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, SP, Brazil ; Departamento de Genética e Biologia Evolutiva, IB-Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Gustavo M
authors.initials: GM
authors.lastname: Silva
authors.affiliation: Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Adrian
authors.initials: A
authors.lastname: Hand
authors.affiliation: Departamento de Física Experimental, IF-Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Cristiano L P
authors.initials: CL
authors.lastname: de Oliveira
authors.affiliation: Departamento de Física Experimental, IF-Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Renata N
authors.initials: RN
authors.lastname: Bicev
authors.affiliation: Instituto de Química, UNICAMP, Campinas, SP, Brazil.
authors.forename: Fabio
authors.initials: F
authors.lastname: Gozzo
authors.affiliation: Departamento de Microbiologia, ICB-Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Mario H
authors.initials: MH
authors.lastname: Barros
authors.affiliation: Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, SP, Brazil ; Departamento de Genética e Biologia Evolutiva, IB-Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Janaina M M
authors.initials: JM
authors.lastname: Leme
authors.affiliation: Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Erina
authors.initials: E
authors.lastname: Ohara
mesh_terms: D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*
chemical_list: D046988:Proteasome Endopeptidase Complex; D005978:Glutathione
keywords: 20SPT, 20S proteasome core particle; 26SPT, 26S proteasome; GSH, reduced glutathione; GSSG, oxidized glutathione; Oxidized proteins; Proteasomal gating; Proteasome; ROS, reactive oxygen species; Redox regulation; S-glutathionylation; SAXS, small angle X-rays scattering; TEM, transmission electron microscopy