Topic: protein quality control

Proliferation of malignant cell also depends on high rate of protein synthesis that increases demands on protein quality control mechanisms. Quality of intracellular proteins are controlled at the level of both endoplasmic reticulum (ER) and 26S proteasome. Disturbances in the functions of either ER or proteasome are associated with particular stress responses. The cellular response to ER stress involves translation inhibition, expression of ER chaperones and degradation of aberrant protein. Elevated expression of HSP70 that binds aberrant proteins or supports their translocation to lysosomes

The KCNH2 gene-encoded KV11.1 voltage-gated potassium channel, also known as hERG, is abundantly expressed in the heart and brain, and plays an essential role in stabilizing cardiac and neuronal membrane potentials. Loss-of-function KCNH2 mutations, as well as pharmacological suppressions of human KV11.1 channel function, have been associated with arrhythmia and epilepsy. The majority of disease-related mutations involve aberrant KV11.1 protein folding, resulting in enhanced endoplasmic reticulum (ER)-associated degradation and decreased cell-surface protein level. Despite previous identificat