General Information:

Id: 560
Diseases: Parkinson disease
Homo sapiens
BTO:0000793 SH-SY5Y cell
article
Reference: Olzmann JA et al.(2007) Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6. J. Cell Biol. 178: 1025-1038 [PMID: 17846173]

Interaction Information:

Comment L166P mutant DJ-1, but not wild-type DJ-1, was able to coprecipitate Myc-tagged parkin.
Formal Description
Interaction-ID: 2902

gene/protein

PARK7

NOT interacts (colocalizes) with

gene/protein

PARK2

Drugbank entries Show/Hide entries for PARK7
Comment L166P mutant DJ-1, but not wild-type DJ-1, was able to coprecipitate Myc-tagged parkin.
Formal Description
Interaction-ID: 2903

gene/protein mutant

PARK7-p.L166P

interacts (colocalizes) with

gene/protein

PARK2

Comment HSP70 did not associate with DJ-1 mutant L166P.
Formal Description
Interaction-ID: 2905

gene/protein mutant

PARK7-p.L166P

NOT interacts (colocalizes) with

gene/protein

HSPA1A

Drugbank entries Show/Hide entries for HSPA1A
Comment Parkin ubiquitinates DJ-1 mutant L166P, but not wild-type DJ-1, suggesting that parkin selectively recognizes and ubiquitinates misfolded DJ-1.
Formal Description
Interaction-ID: 2909

gene/protein

PARK2

increases_ubiquitination/sumoylation of

gene/protein mutant

PARK7-p.L166P

Comment Parkin ubiquitinates DJ-1 mutant L166P, but not wild-type DJ-1, suggesting that parkin selectively recognizes and ubiquitinates misfolded DJ-1.
Formal Description
Interaction-ID: 2911

gene/protein

PARK2

NOT increases_ubiquitination/sumoylation of

gene/protein

PARK7

Drugbank entries Show/Hide entries for PARK7
Comment Even at extremely high levels of overexpression, parkin was unable to promote degradation of L166P mutant or wild-type DJ-1.
Formal Description
Interaction-ID: 2913

gene/protein

PARK2

NOT decreases_quantity of

gene/protein mutant

PARK7-p.L166P

via ubiquitin-mediated proteasomal degradation
Comment Even at extremely high levels of overexpression, parkin was unable to promote degradation of L166P mutant or wild-type DJ-1.
Formal Description
Interaction-ID: 2915

gene/protein

PARK2

NOT decreases_quantity of

gene/protein

PARK7

via ubiquitin-mediated proteasomal degradation
Drugbank entries Show/Hide entries for PARK7
Comment K48-linked polyubiquitination acts as the canonical signal for targeting the substrate to the proteasome for degradation. In contrast, K63-linked polyubiquitination has recently been shown to have a proteasome-independent role in the regulation of several cellular processes.
Formal Description
Interaction-ID: 2916
Comment K48-linked polyubiquitination acts as the canonical signal for targeting the substrate to the proteasome for degradation. In contrast, K63-linked polyubiquitination has recently been shown to have a proteasome-independent role in the regulation of several cellular processes.
Formal Description
Interaction-ID: 2917
Comment UBCh13, which catalyzes K63-linked ubiquitination, interacts with Parkin.
Formal Description
Interaction-ID: 2922

gene/protein

UBE2N

interacts (colocalizes) with

gene/protein

PARK2

Comment Parkin interacts with UBCh7 and UBCh8, but not with UBCh5.
Formal Description
Interaction-ID: 2923

gene/protein

PARK2

interacts (colocalizes) with

gene/protein

UBE2G2

Comment Parkin interacts with UBCh7 and UBCh8, but not with UBCh5.
Formal Description
Interaction-ID: 2928

gene/protein

PARK2

interacts (colocalizes) with

gene/protein

UBE2H

Comment Parkin interacts with UBCh7 and UBCh8, but not with UBCh5.
Formal Description
Interaction-ID: 2929

gene/protein

PARK2

NOT interacts (colocalizes) with

gene/protein

UBE2D1

Comment UBCh13, which catalyzes K63-linked ubiquitination, interacts with Parkin.
Formal Description
Interaction-ID: 2935

gene/protein

UBE2N

increases_activity of

Comment Parkin facilitates K63-linked polyubiquitination of L166P mutant DJ-1 in cooperation with UBC13-UEV1a complex.
Formal Description
Interaction-ID: 2939

gene/protein

PARK2

increases_activity of

of PARK7-L166P , together with UBC13-UEV1a complex
Comment Parkin was able to facilitate the polyubiquitination of L166P mutant DJ-1 in the presence of wild-type ubiquitin and ubiquitin mutant Ub-K63.
Formal Description
Interaction-ID: 2940

gene/protein

PARK2

increases_ubiquitination/sumoylation of

gene/protein mutant

PARK7-p.L166P

via K63-linked ubiquitin chains
Comment Treatment with the proteasome inhibitor MG132 caused a dramatic relocation of L166P mutant DJ-1 and parkin to a single prominent, perinuclear inclusion.
Formal Description
Interaction-ID: 2941

gene/protein mutant

PARK7-p.L166P

is localized in

cellular component

aggresome

after treatment with proteasome inhibitor MG132
Comment Treatment with the proteasome inhibitor MG132 caused a dramatic relocation of L166P mutant DJ-1 and parkin to a single prominent, perinuclear inclusion.
Formal Description
Interaction-ID: 2942

gene/protein

PARK2

is localized in

cellular component

aggresome

after treatment with proteasome inhibitor MG132
Comment Recruitment of L166P mutant DJ-1 to the aggresome is dependent on intact microtubules.
Formal Description
Interaction-ID: 2943

increases_transport of

gene/protein mutant

PARK7-p.L166P

into aggresome
Comment Parkin selectively promotes the recruitment of L166P mutant DJ-1, but not wild-type DJ-1, to aggresomes.
Formal Description
Interaction-ID: 2944

gene/protein

PARK2

increases_transport of

gene/protein mutant

PARK7-p.L166P

into aggresome
Comment Parkin selectively promotes the recruitment of L166P mutant DJ-1, but not wild-type DJ-1, to aggresomes.
Formal Description
Interaction-ID: 2945

gene/protein

PARK2

NOT increases_transport of

gene/protein

PARK7

into aggresome
Drugbank entries Show/Hide entries for PARK7
Comment K63-linked polyubiquitination of misfolded DJ-1 by parkin promotes aggresome formation.
Formal Description
Interaction-ID: 2946

increases_activity of

Comment HDAC6 does not bind nonubiquitinated L166P mutant DJ-1 in untreated cells. In contrast, HDAC6 strongly interacts with polyubiquitinated L166P mutant DJ-1 induced by parkin coexpression in MG132-treated cells.
Formal Description
Interaction-ID: 2947

gene/protein

HDAC6

interacts (colocalizes) with

gene/protein mutant

PARK7-p.L166P

if PARK7-p.L166P is polyubiquitinated
Drugbank entries Show/Hide entries for HDAC6
Comment HDAC6 increases transport of DJ-1 to aggresomes.
Formal Description
Interaction-ID: 10117

gene/protein

HDAC6

increases_transport of

gene/protein

PARK7

into aggresome
Drugbank entries Show/Hide entries for HDAC6 or PARK7