The proteasome activator PA200 regulates tumor cell responsiveness to glutamine and resistance to ionizing radiation.

ABSTRACT: The cellular response to ionizing radiation (IR) involves a variety of mechanisms to repair damage and maintain cell survival. We previously reported that the proteasome activator PA200 promotes long-term cell survival after IR exposure. The molecular function of PA200 is to enhance proteasome-mediated cleavage after glutamate; however, it is not known how this molecular function promotes survival after IR exposure. Here, we report that upon IR exposure, cellular demand for exogenous glutamine is increased. Cells containing PA200 are capable of surviving this IR-induced glutamine demand, whereas PA200-deficient cells show impaired long-term survival. Additional glutamine supplementation reverses the radiosensitivity of PA200-knockdown cells suggesting impaired glutamine homeostasis in thes

SUBMITTER: Blickwedehl J 

PROVIDER: S-EPMC5261820 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature