TY  - JOUR
AU  - Ukmar-Godec, Tina
AU  - Fang, P.
AU  - Ibanez de Opakua, Alain
AU  - Henneberg, F.
AU  - Godec, A.
AU  - Pan, K.-T.
AU  - Cima Omori, Maria Sol
AU  - Chari, A.
AU  - Mandelkow, Eckhard
AU  - Urlaub, H.
AU  - Zweckstetter, Markus
TI  - Proteasomal degradation of the intrinsically disordered protein tau at single-residue resolution
JO  - Science advances
VL  - 6
IS  - 30
SN  - 2375-2548
CY  - Washington, DC [u.a.]
PB  - Assoc.
M1  - DZNE-2020-01280
SP  - eaba3916 -
PY  - 2020
AB  - Intrinsically disordered proteins (IDPs) can be degraded in a ubiquitin-independent process by the 20S proteasome. Decline in 20S activity characterizes neurodegenerative diseases. Here, we examine 20S degradation of IDP tau, a protein that aggregates into insoluble deposits in Alzheimer’s disease. We show that cleavage of tau by the 20S proteasome is most efficient within the aggregation-prone repeat region of tau and generates both short, aggregation-deficient peptides and two long fragments containing residues 1 to 251 and 1 to 218. Phosphorylation of tau by the non-proline–directed Ca2+/calmodulin-dependent protein kinase II inhibits degradation by the 20S proteasome. Phosphorylation of tau by GSK3β, a major proline-directed tau kinase, modulates tau degradation kinetics in a residue-specific manner. The study provides detailed insights into the degradation products of tau generated by the 20S proteasome, the residue specificity of degradation, single-residue degradation kinetics, and their regulation by posttranslational modification.
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC7439447
C6  - pmid:32832664
DO  - DOI:10.1126/sciadv.aba3916
UR  - https://pub.dzne.de/record/153283
ER  -