PKCε SUMOylation Is Required for Mediating the Nociceptive Signaling of Inflammatory Pain.

Despite the important roles of protein kinase Cε and transient receptor potential vanilloind 1 (TRPV1) in inflammatory hypersensitivity, how is involved in the regulation of thermal hyperalgesia is not fully understood. We report here that duanyu1531ε is SUMOylated at a C-terminal lysine residue (K534), which enhances the sensitivity of the TRPV1 channel. We demonstrate that duanyu1531ε phosphorylation promotes its SUMOylation, which in turn regulates the phosphorylation level of TRPV1 serine 800 residue via controlling the binding of duanyu1531ε and TRPV1 and increased duanyu1531ε kinase activity. More importantly, the reduced ability of duanyu1531ε knockdown mice to develop inflammatory thermal hyperalgesia was rescued by viral infection of lumbar 4/5 dorsal root ganglia neurons of wild-type but not the SUMOylation-deficient duanyu1531ε mutant. Therefore, the SUMOylation of duanyu1531ε potentiates inflammatory thermal hyperalgesia through stabilizing the interaction with TRPV1 to enhance its function by phosphorylation.

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