SEPT5_v2 is a parkin-binding protein.
Mutations in parkin are associated with various inherited forms of Parkinson's disease (PD). Parkin is a ubiquitin ligase enzyme that catalyzes the covalent attachment of ubiquitin moieties onto substrate proteins destined for proteasomal degradation. The substrates of parkin-mediated ubiquitination have yet to be completely identified. Using a yeast two-hybrid screen, we isolated the septin, human SEPT5_v2 (also known as cell division control-related protein 2), as a putative parkin-binding protein. SEPT5_v2 is highly homologous to another septin, SEPT5, which was recently identified as a target for parkin-mediated ubiquitination. SEPT5_v2 binds to parkin at the amino terminus and in the ring finger domains. Several lines of evidence have validated the putative link between parkin and SEPT5_v2. Parkin co-precipitates with SEPT5_v2 from human substantia nigra lysates. Parkin ubiquitinates SEPT5_v2 in vitro, and both SEPT5_v1 and SEPT5_v2 accumulate in brains of patients with ARJP, suggesting that parkin is essential for the normal metabolism of these proteins. These findings suggest that an important relationship exists between parkin and septins.
Choi
P
P
Department of Pharmacology, Loyola University Medical Center, Bldg 102/3634, 2160 S 1st Ave, Maywood, IL 60153, USA.
Snyder
H
H
Petrucelli
L
L
Theisler
C
C
Chong
M
M
Zhang
Y
Y
Lim
K
K
Chung
K K K
KK
Kehoe
K
K
D'Adamio
L
L
Lee
J M
JM
Cochran
E
E
Bowser
R
R
Dawson
T M
TM
Wolozin
B
B
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007668:Kidney; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009447:Neuroblastoma; D010300:Parkinson Disease / Q000378:metabolism; D010957:Plasmids; D011233:Precipitin Tests; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D014157:Transcription Factors; D025801:Ubiquitin; D051841:Transcription Factor RelB; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein