Parkin interacts with the proteasome subunit alpha4.
Mutations in the parkin gene encoding an E3 ligase are responsible for autosomal recessive Parkinson's disease. Putative parkin substrates and interacting partners have been identified, but the molecular mechanism underlying parkin-related neurodegeneration is still unclear. We have identified the 20S proteasomal subunit alpha4 (synonyms: PSMA7, XAPC7, subunit alpha type 7) as a new interacting partner of parkin. The C-terminal IBR-RING domain of parkin and the C-terminal part of alpha4 were essential for the interaction. Biochemical studies revealed that alpha4 was not a substrate for parkin-dependent ubiquitylation. Putative functions of the interaction might therefore be substrate presentation to the proteasome or regulation of proteasomal activity. Full-length parkin and parkin lacking the N-terminal ubiquitin-like domain slightly increased the proteasomal activity in HEK 293T cells, in line with the latter hypothesis.
Dächsel
J C
JC
Labor für Molekulare Neurogenetik, Neurologische Klinik der Ludwig-Maximilians-Universität, Marchioninistr. 15, 81377 München, Germany.
Lücking
C B
CB
Deeg
S
S
Schultz
E
E
Lalowski
M
M
Casademunt
E
E
Corti
O
O
Hampe
C
C
Patenge
N
N
Vaupel
K
K
Yamamoto
A
A
Dichgans
M
M
Brice
A
A
Wanker
E E
EE
Kahle
P J
PJ
Gasser
T
T
D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008957:Models, Genetic; D009097:Multienzyme Complexes / Q000737:chemistry; D009154:Mutation; D016716:PC12 Cells; D010957:Plasmids / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*
D018076:DNA, Complementary; D009097:Multienzyme Complexes; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C488661:alpha4 subunit, proteasome 20S, human