title: TRPA1 is a substrate for de-ubiquitination by the tumor suppressor CYLD.
abstract: 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.
authors.affiliation: Laboratory of Cell Biology and Immunology, Center for Biomedical Research at Queen's Medical Center, Honolulu, HI 96813, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stokes
authors.forename: Clay
authors.initials: C
authors.lastname: Wakano
authors.forename: Murielle
authors.initials: M
authors.lastname: Koblan-Huberson
authors.forename: Chaker N
authors.initials: CN
authors.lastname: Adra
authors.forename: Andrea
authors.initials: A
authors.lastname: Fleig
authors.forename: Helen
authors.initials: H
authors.lastname: Turner
mesh_terms: 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*
chemical_list: 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