Investigation of Novel Functions of KICSTOR Components in the DNA Damage Response

The mechanistic target of rapamycin complex (mTOR) is an atypical serine/threonine kinase which acts as a global cellular regulator of growth and cell survival in response to environmental cues and is a member of the phosphoinositide 3-kinase (PI3K)-related kinase family. Through the numerous inhibitions and initiations of catabolic and anabolic processes respectively, mTORC1 is also a major promoter for cell-cycle progression. mTORC1 can be activated by growth factors such as insulin as a downstream target of PI3K signaling. It is expressed in all somatic cell types plays vital roles in axonal movement, neuronal plasticity and development in the brain. The aberrant activation of mTORC1 has been implicated as one of the leading causes of Tuberous Sclerosis and Focal Epilepsies. Constitutively active mutations in mTOR complex subunits and their upstream signalling proteins have also been documented in over 30% of Cancers, such as the recently recognised links to prostate and colon cancer. Some PI3K/mTOR inhibitors have also been shown to potently inhibit DNA damage responses in non-small cell lung cancer (NSCLC) cell lines suggesting mTOR plays a key role in DNA damage response (DDR) mechanisms. This review focuses on delineating the mTOR pathway, mechanism of mTOR inhibitors and their possible role in inhibiting the DDR mechanism