title: Glatiramer acetate and nanny proteins restrict access of the multiple sclerosis autoantigen myelin basic protein to the 26S proteasome.
abstract: We recently showed that myelin basic protein (MBP) is hydrolyzed by 26S proteasome without ubiquitination. The previously suggested concept of charge-mediated interaction between MBP and the proteasome led us to attempt to compensate or mimic its positive charge to inhibit proteasomal degradation. We demonstrated that negatively charged actin and calmodulin (CaM), as well as basic histone H1.3, inhibit MBP hydrolysis by competing with the proteasome and MBP, respectively, for binding their counterpart. Interestingly, glatiramer acetate (GA), which is used to treat multiple sclerosis (MS) and is structurally similar to MBP, inhibits intracellular and in vitro proteasome-mediated MBP degradation. Therefore, the data reported in this study may be important for myelin biogenesis in both the normal state and pathophysiological conditions.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, V-437, Moscow 117871, Russia ; Chemistry Department, Lomonosov Moscow State University, Moscow 119991, Russia.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Kuzina
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, V-437, Moscow 117871, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Kudriaeva
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, V-437, Moscow 117871, Russia ; Chemistry Department, Lomonosov Moscow State University, Moscow 119991, Russia ; Kazan Federal University, Kazan, Republic of Tatarstan 420008, Russia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Smirnov
authors.affiliation: Nanotechnology Research and Education Centre RAS, St. Petersburg Academic University, St. Petersburg 194021, Russia.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Dubina
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, V-437, Moscow 117871, Russia ; Chemistry Department, Lomonosov Moscow State University, Moscow 119991, Russia ; Kazan Federal University, Kazan, Republic of Tatarstan 420008, Russia ; Institute of Gene Biology, Russian Academy of Sciences, Moscow 117334, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gabibov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, V-437, Moscow 117871, Russia ; Kazan Federal University, Kazan, Republic of Tatarstan 420008, Russia ; Institute of Gene Biology, Russian Academy of Sciences, Moscow 117334, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Belogurov
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D015153:Blotting, Western; D002417:Cattle; D002645:Chickens; D000068717:Glatiramer Acetate; D057809:HEK293 Cells; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D008807:Mice, Inbred BALB C; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects; D034421:Sus scrofa; D014162:Transfection
chemical_list: D001324:Autoantigens; D004676:Myelin Basic Protein; D010455:Peptides; D000068717:Glatiramer Acetate; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease