Regulation and functions of clusterin: A protector against stress

Radiation therapy is a common treatment for many types of tumors. Therefore, it is vital to understand the cellular responses to radiotherapy in malignant cells, as well as the surrounding normal tissues in order to optimize antitumor efficacy. Clusterin (CLU) is a secreted glycoprotein that has been implicated in many normal biological processes as well as many pathological diseases, including cancer. Our laboratory identified the secreted form of clusterin (sCLU) as a protein/transcript that could be induced by doses of ionizing radiation (IR) as low as 0.02 Gy, suggesting a role for sCLU in the cellular response to IR. While the exact functions of CLU are complex, it has been suggested that sCLU, the fully processed and glycosylated form of the CLU protein, plays a role in cytoprotection after cellular stress. sCLU appears to provide cytoprotection against cellular injury and inflammatory responses potentially by acting as a molecular chaperone, clearing cellular debris or binding to inflammatory and growth suppressive cytokines, such as TGF-β1. A better understanding of this protein and its various roles in cellular responses to stress will allow us to generate better treatments and therapies for many different pathological processes. The functions of sCLU and its role(s) in disease processes will be discussed.