FADD's importance in embryogenesis and lymphocyte death response has been known, but the mechanism that underlies these functions in FADD has remained elusive.
Researchers found that mice that did not express FADD contained raised levels of RIP1, Receptor-Interacting Protein 1, an important protein that mediates necrosis and the apoptotic processes, and their embryonic development failed due to massive necrosis.
"When the FADD-mediated death process is deregulated, we will produce white bloods cells that will attack our own tissue, which is the cause of auto-immune diseases, such as arthritis and lupus," said Dr. Zhang. "And without the necessary cell deaths that are required for tumor surveillance, humans could develop cancer."
There are drugs currently under development today that activate TNF-a-related apoptosis-inducing ligand (TRAIL) death receptor signaling, which induces apoptosis through FADD in cancer cells specifically, but its mechanisms are not well understood and the treatment not perfected. There are also tumor cells that are resistant to TRAIL-induced apoptosis for unknown causes.
"The killing of these tumor cells is not efficient, and this paper actually figured out why," said Dr. Zhang. "We now know that the FADD protein, while required for apoptotic death, is inhibiting necrotic death in tumor cells."
|Contact: Steve Graff|
Thomas Jefferson University