TRPA1 is a substrate for de-ubiquitination by the tumor suppressor CYLD.
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.
Stokes
Alexander
A
Laboratory of Cell Biology and Immunology, Center for Biomedical Research at Queen's Medical Center, Honolulu, HI 96813, USA.
Wakano
Clay
C
Koblan-Huberson
Murielle
M
Adra
Chaker N
CN
Fleig
Andrea
A
Turner
Helen
H
D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism; D000074749:Deubiquitinating Enzyme CYLD; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D013379:Substrate Specificity; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD