| First Author | Burikhanov R | Year | 2009 |
| Journal | Cell | Volume | 138 |
| Issue | 2 | Pages | 377-88 |
| PubMed ID | 19632185 | Mgi Jnum | J:151977 |
| Mgi Id | MGI:4355647 | Doi | 10.1016/j.cell.2009.05.022 |
| Citation | Burikhanov R, et al. (2009) The tumor suppressor Par-4 activates an extrinsic pathway for apoptosis. Cell 138(2):377-88 |
| abstractText | Prostate apoptosis response-4 (Par-4) is a proapoptotic protein with intracellular functions in the cytoplasm and nucleus. Unexpectedly, we noted Par-4 protein is spontaneously secreted by normal and cancer cells in culture, and by Par-4 transgenic mice that are resistant to spontaneous tumors. Short exposure to endoplasmic reticulum (ER) stress-inducing agents further increased cellular secretion of Par-4 by a brefeldin A-sensitive pathway. Secretion occurred independently of caspase activation and apoptosis. Interestingly, extracellular Par-4 induced apoptosis by binding to the stress response protein, glucose-regulated protein-78 (GRP78), expressed at the surface of cancer cells. The interaction of extracellular Par-4 and cell surface GRP78 led to apoptosis via ER stress and activation of the FADD/caspase-8/caspase-3 pathway. Moreover, apoptosis inducible by TRAIL, which also exerts cancer cell-specific effects, is dependent on extracellular Par-4 signaling via cell surface GRP78. Thus, Par-4 activates an extrinsic pathway involving cell surface GRP78 receptor for induction of apoptosis. |
