General Information:

Id: 268
Diseases: Parkinson disease
Homo sapiens
BTO:0000793 SH-SY5Y cell
article
Reference: Ko HS et al.(2009) CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity. Proc. Natl. Acad. Sci. U.S.A. 106: 2897-2902 [PMID: 19196961]

Interaction Information:

Comment LRRK2 interacts with Hsp70-interacting protein CHIP.
Formal Description
Interaction-ID: 1090

gene/protein

LRRK2

interacts (colocalizes) with

gene/protein

STUB1

Comment LRRK2 mutation R1441C and G2019S interact with CHIP.
Formal Description
Interaction-ID: 1091

gene/protein mutant

LRRK2-p.R1441C

interacts (colocalizes) with

gene/protein

STUB1

Comment LRRK2 mutation R1441C and G2019S interact with CHIP.
Formal Description
Interaction-ID: 1092

gene/protein mutant

LRRK2-p.G2019S

interacts (colocalizes) with

gene/protein

STUB1

Comment CHIP ubiquitinates LRRK2.
Formal Description
Interaction-ID: 1094

gene/protein

STUB1

increases_ubiquitination/sumoylation of

gene/protein

LRRK2

Comment CHIP promotes the ubiquitin proteasomal degradation of LRRK2 and LRRK2 mutants R1441C and G2019S.
Formal Description
Interaction-ID: 1095

gene/protein

STUB1

decreases_quantity of

gene/protein

LRRK2

via ubiquitin-mediated proteasomal degradation
Comment CHIP promotes the ubiquitin proteasomal degradation of LRRK2 and LRRK2 mutants R1441C and G2019S.
Formal Description
Interaction-ID: 1096

gene/protein

STUB1

decreases_quantity of

gene/protein mutant

LRRK2-p.R1441C

via ubiquitin-mediated proteasomal degradation
Comment CHIP promotes the ubiquitin proteasomal degradation of LRRK2 and LRRK2 mutants R1441C and G2019S.
Formal Description
Interaction-ID: 1097

gene/protein

STUB1

decreases_quantity of

gene/protein mutant

LRRK2-p.G2019S

via ubiquitin-mediated proteasomal degradation
Comment In contrast to LRRK2-WT, the R1441C and G2019S mutants of LRRK2 cause significant cell toxicity.
Formal Description
Interaction-ID: 1099

gene/protein mutant

LRRK2-p.R1441C

increases_activity of

process

neuron death

Comment In contrast to LRRK2-WT, the R1441C and G2019S mutants of LRRK2 cause significant cell toxicity.
Formal Description
Interaction-ID: 1100

gene/protein mutant

LRRK2-p.G2019S

increases_activity of

process

neuron death

Comment CHIP reduces LRRK2-R1441C and LRRK2-G2019S induced cell toxicity. This indicates that CHIP influences LRRK2 toxicity by regulating LRRK2 protein levels.
Formal Description
Interaction-ID: 1102

gene/protein

STUB1

decreases_activity of

process

neuron death

incuced by LRRK2 mutants
Comment CHIP reduces LRRK2-R1441C and LRRK2-G2019S induced cell toxicity. This indicates that CHIP influences LRRK2 toxicity by regulating LRRK2 protein levels.
Formal Description
Interaction-ID: 3742

gene/protein

STUB1

decreases_activity of

gene/protein mutant

LRRK2-p.G2019S

Comment CHIP reduces LRRK2-R1441C and LRRK2-G2019S induced cell toxicity. This indicates that CHIP influences LRRK2 toxicity by regulating LRRK2 protein levels.
Formal Description
Interaction-ID: 3743

gene/protein

STUB1

decreases_activity of

gene/protein mutant

LRRK2-p.R1441C

Comment Treatment with 17AAG, a HSP90 inhibitor, significantly protected against G2019S- and R1441C-LRRK2 mutant-induced cell death.
Formal Description
Interaction-ID: 3749

drug/chemical compound

17AAD

decreases_activity of

gene/protein mutant

LRRK2-p.G2019S

Comment Treatment with 17AAG, a HSP90 inhibitor, significantly protected against G2019S- and R1441C-LRRK2 mutant-induced cell death.
Formal Description
Interaction-ID: 3750

drug/chemical compound

17AAD

decreases_activity of

gene/protein mutant

LRRK2-p.R1441C

Comment Treatment with 17AAG, a HSP90 inhibitor, significantly protected against G2019S- and R1441C-LRRK2 mutant-induced cell death.
Formal Description
Interaction-ID: 3751

drug/chemical compound

17AAD

decreases_activity of

process

neuron death

induced by LRRK2 mutants
Comment CHIP promotes the ubiquitin proteasomal degradation of LRRK2 and LRRK2 mutants R1441C and G2019S.
Formal Description
Interaction-ID: 13601

gene/protein

STUB1

increases_activity of

thus increasing the degradation of LRRK2 and LRRK2 mutants R1441C and G2019S