Doxorubicin induces caspase-mediated proteolysis of KV7.1.

ABSTRACT: K_v7.1 (KCNQ1) coassembles with KCNE1 to generate the cardiac I_Ks -channel. Gain- and loss-of-function mutations in KCNQ1 are associated with cardiac arrhthymias, highlighting the importance of modulating I_Ks activity for cardiac function. Here, we report proteolysis of K_v7.1 as an irreversible posttranslational modification. The identification of two C-terminal fragments of K_v7.1 led us to identify an aspartate critical for the generation of one of the fragments and caspases as responsible for mediating proteolysis. Activating caspases reduces K_v7.1/KCNE1 currents, which is abrogated in cells expressing caspase-resistant channels. Enhanced cleavage of K_v7.1 can be detected for the LQT mutation G460S,

SUBMITTER: Strigli A 

PROVIDER: S-EPMC6162258 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature