Cell Signal. 2006 Oct;18(10):1584-94. Epub 2006 Feb 23.
TRPA1 is a substrate for de-ubiquitination by the tumor suppressor CYLD.
Stokes, A., Wakano, C., Koblan-Huberson, M., Adra, C. N., Fleig, A., Turner, H.,
["Laboratory of Cell Biology and Immunology, Center for Biomedical Research at Queen's Medical Center, Honolulu, HI 96813, USA."]
["Laboratory of Cell Biology and Immunology, Center for Biomedical Research at Queen's Medical Center, Honolulu, HI 96813, USA."]
Certain TRP cation channels confer the ability to sense environmental stimuli (heat, cold, pressure, osmolarity) across physiological and pathophysiological ranges. TRPA1 is a TRP-related channel that responds to cold temperatures, and pungent compounds that include the cold-mimetic icilin and cannabinoids. The initial report of TRPA1 as a transformation-associated gene product in lung epithelia is at odds with subsequent descriptions of a tissue distribution for TRPA1 that is restricted to sensory neurons. Here, we report that the human TRPA1 protein is widely expressed outside the CNS, and is indeed dys-regulated during oncogenic transformation. We describe that TRPA1 associates with the tumor-suppressor protein CYLD. TRPA1 is a novel substrate for the de-ubiquitinating activity of CYLD, and this de-ubiquitination has the net effect of increasing the cellular pool of TRPA1 proteins. Oncogenic mutations in the CYLD gene may therefore be predicted to alter cellular levels of TRPA1.
PMID: 16500080
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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Screening
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| Experimental screening | Non-experimental screening | Reference | ||||||||
| TRP channel construct | Interactor source | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
| TRPA1 |
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CYLD | Inference | Prediction | 16500080 | |||||
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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top
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| Validation: In vivo validation
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|---|---|---|---|---|---|---|---|---|---|---|
| Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
| Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPA1 |
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CYLD | Co-immunoprecipitation | HEK293 | Human | Full-length | Human | Full-length | 16500080 | |
| TRPA1 |
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CYLD | Co-immunoprecipitation | MDA-MB-435 | Not used | Human | Full-length | 16500080 | ||
| TRPA1 |
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CYLD | Co-immunoprecipitation | Human Jurkat T cell | 16500080 | |||||
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
|
Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
|
top
|
| Functional consequence
|
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|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
| TRPA1 |
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CYLD | In vivo PTM assay | De-ubiquitination | 16500080 | |||||||
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)