Protein quality control of thermosensitive nuclear transport factor importin α

Intracellular proteins have a wide range of thermal stabilities; some are very sensitive to temperature and can be denatured even in normal physiological conditions. Here, we show that members of the nuclear transport factor importin α family have a variety of thermosensitivities, and some subtypes can be denatured at physiological temperature. The thermal stabilities of importin α subtypes changed remarkably depending on their binding partners. Proteomic analyses of importin α-interacting proteins in the cytoplasm revealed that continuous nuclear transport cycles help maintain importin α quality. Additionally, in senescent cells, the proportions of denatured thermosensitive importin α subtypes increased, indicating that a low transport rate leads to further inhibition of transport efficiency. The denaturing temperatures of importin α family members correlate with the body temperatures of the animals in which they are present, thus their thermosensitivity might be important for heat stress response and other cellular functions related to aging and growth.