title: Tau protein degradation is catalyzed by the ATP/ubiquitin-independent 20S proteasome under normal cell conditions.
abstract: Tau is the major protein exhibiting intracellular accumulation in Alzheimer disease. The mechanisms leading to its accumulation are not fully understood. It has been proposed that the proteasome is responsible for degrading tau but, since proteasomal inhibitors block both the ubiquitin-dependent 26S proteasome and the ubiqutin-independent 20S proteasome pathways, it is not clear which of these pathways is involved in tau degradation. Some involvement of the ubiquitin ligase, CHIP in tau degradation has also been postulated during stress. In the current studies, we utilized HT22 cells and tau-transfected E36 cells in order to test the relative importance or possible requirement of the ubiquitin-dependent 26S proteasomal system versus the ubiquitin-independent 20S proteasome, in tau degradation. By means of ATP-depletion, ubiquitinylation-deficient E36ts20 cells, a 19S proteasomal regulator subunit MSS1-siRNA approaches, and in vitro ubiquitinylation studies, we were able to demonstrate that ubiquitinylation is not required for normal tau degradation.
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany. grune@uni-hohenheim.de
authors.forename: Tilman
authors.initials: T
authors.lastname: Grune
authors.forename: Diana
authors.initials: D
authors.lastname: Botzen
authors.forename: Martina
authors.initials: M
authors.lastname: Engels
authors.forename: Peter
authors.initials: P
authors.lastname: Voss
authors.forename: Barbara
authors.initials: B
authors.lastname: Kaiser
authors.forename: Tobias
authors.initials: T
authors.lastname: Jung
authors.forename: Stefanie
authors.initials: S
authors.lastname: Grimm
authors.forename: Gennady
authors.initials: G
authors.lastname: Ermak
authors.forename: Kelvin J A
authors.initials: KJ
authors.lastname: Davies
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D066298:In Vitro Techniques; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D061988:Proteasome Inhibitors; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D061988:Proteasome Inhibitors; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D025801:Ubiquitin; D016875:tau Proteins; D000255:Adenosine Triphosphate; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C119011:26S proteasome non-ATPase regulatory subunit 13