Prof. Sarit Larisch
Department of Human Biology
Our lab focuses on investigating the molecular mechanisms of cell death, and how abnormal regulation of this process contributes to human diseases. We identified a mitochondrial pro-apoptotic protein termed ARTS (Sept4_i2) that is derived from the Sept4 septin gene by differential splicing. Over-expression of ARTS is sufficient to promote apoptosis in many cultured tumor cells. Conversely, the reduction of endogenous ARTS protein by anti-sense or shRNA methods can protect cells against various pro-apoptotic insults. This indicates that ARTS is important for induction of apoptosis in a wide variety of apoptosis paradigms. A central step for the execution of apoptosis is the activation of caspases, a family of enzymes that when activated bring about the demise of the cell. Caspases are regulated by both activators and inhibitors, such as IAPs (Inhibitor of Apoptosis Proteins). The best characterized member of this family is X-IAP (X-linked IAP). ARTS is located at the mitochondrial outer membrane (MOM) in living cells, but in response to pro-apoptotic stimuli it translocates to the cytosol. This permits ARTS to bind and inhibit XIAP, thereby initiating caspase activation and apoptosis.