title: Multiple sclerosis autoantigen myelin basic protein escapes control by ubiquitination during proteasomal degradation.
abstract: The vast majority of cellular proteins are degraded by the 26S proteasome after their ubiquitination. Here, we report that the major component of the myelin multilayered membrane sheath, myelin basic protein (MBP), is hydrolyzed by the 26S proteasome in a ubiquitin-independent manner both in vitro and in mammalian cells. As a proteasomal substrate, MBP reveals a distinct and physiologically relevant concentration range for ubiquitin-independent proteolysis. Enzymatic deimination prevents hydrolysis of MBP by the proteasome, suggesting that an abnormally basic charge contributes to its susceptibility toward proteasome-mediated degradation. To our knowledge, our data reveal the first case of a pathophysiologically important autoantigen as a ubiquitin-independent substrate of the 26S proteasome.
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117871 Moscow V-437, Russia, the Institute of Gene Biology, Russian Academy of Sciences, 117334 Moscow, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Belogurov
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117871 Moscow V-437, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Kudriaeva
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117871 Moscow V-437, Russia, the Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia, and.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Kuzina
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117871 Moscow V-437, Russia, the Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia, and.
authors.forename: Ivan
authors.initials: I
authors.lastname: Smirnov
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117871 Moscow V-437, Russia.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Bobik
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117871 Moscow V-437, Russia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Ponomarenko
authors.affiliation: the Cancer and Vascular Biology Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Kravtsova-Ivantsiv
authors.affiliation: the Cancer and Vascular Biology Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel c_tzachy@netvision.net.il.
authors.forename: Aaron
authors.initials: A
authors.lastname: Ciechanover
authors.affiliation: From the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117871 Moscow V-437, Russia, the Institute of Gene Biology, Russian Academy of Sciences, 117334 Moscow, Russia, the Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia, and gabibov@mx.ibch.ru.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gabibov
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009103:Multiple Sclerosis; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D054875:Ubiquitination
chemical_list: D001324:Autoantigens; D004676:Myelin Basic Protein; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease
keywords: Antigen Processing; Autoimmune Disease; Multiple Sclerosis; Myelin; Oligodendrocyte; Proteasome; Ubiquitin
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