Fas-Associating protein with Death Domain (also called MORT 1).
Fas (also called CD95 and Apo1) is one of the best characterized death receptors which is activated by binding of its natural ligand FasL (CD95L) or specific anti-Fas monoclonal antibodies. Fas activation plays an important role in many types of physiologic apoptosis, particularly in the immune system. Upon binding to its ligand, Fas recruits the adaptor protein FADD as well as caspase-8, forming the so called DISC. In the DISC, caspase-8 oligomerizes, is auto-activated and then activates downstream effector caspases such as caspase-3- committing the cell to apoptosis. More...
Fas ligand (FasL also CD95L) is the natural ligand of the Fas (CD95) receptor. Like other TNF family members, FasL is a homotrimeric molecule. Each FasL trimer binds three Fas receptor molecules and thereby leads to the trimerization of the Fas receptor initiating the formation of the DISC. More...
Ferredoxin reductase (FR)
Ferredoxin reductase (FR) has been identified to be upregulated in a p53 dependent manner during 5-FU induced apoptosis (Hwang et al., 2001, Nat. Med., 7(10): 1111-1117). FR is the sole mammalian mitochondrial cytochrome P-450 NADPH reductase, and is located on the matrix side of the inner mitochondrial membrane. FR is responsible for transferring electrons from NADPH, via the single electron shuttle ferredoxin, to substrates such as cholesterol. Importantly, under substrate-limiting conditions, electrons can leak from this shuttling system and generate superoxide, and FR has been called an "electron gun". Thus, upregulation of FR might be a source for the generation of reactive oxygen species (ROS) in p53-dependent apoptotic pathways.
Forkhead family transcription factor, mediates transcription of pro-apoptotic genes; it is inactivated by Akt-phosphorylation (Brunet et al., 1999, Cell, 96: 857-68; Kops et al., 1999, Nature, 398: 630-34).
FLice-ASsociated Huge protein (220 kDa): FLASH is a component of the DISC; it contains a motif structurally related to CED-4/Apaf-1 and two tandem-repeated DED homologous domains (DRDs) which mediate its interaction with caspase-8 and FADD. FLASH self-associates through its CED-4-homologous domains (in analogy to CED-4/Apaf-1). FLASH is required for the activation of Caspase-8 during Fas-meditated apoptosis. Overexpression of FLASH deletion mutants inhibited Fas- and TNF-mediated apoptosis. FLASH also interacts with the anti-apoptotic adenovirus protein E1B19K (Imai, 1999, Nature, 398:777-785).
also called MACH or Caspase-8.
FLICE Inhibitor Protein; inhibitor of Death Receptor induced apoptosis; aliases for FLIP are among others Casper, Usurpin, CASH. More...
5-fluorouracil (5-FU) has been in clinical use for several decades and is still the most effective adjuvant therapy for patients with colon cancer. Metabolically, it acts by blocking the enzyme thymidylate synthase and by inhibiting both RNA and DNA synthesis. Like most chemotherapeutic agents, 5-FU induces marked apoptosis in sensitive cells. However, the molecular mechanisms underlying this apoptotic effect is still not well understood, although it appears that 5-FU-mediated apoptosis is p53 dependent. A recent study showed p53-dependent upregulation of ferredoxin reductase following 5-FU treatment, suggesting production of reactive oxygen species (ROS) during the course of 5-FU induced death (Hwang et al., 2001, Nat. Med., 7(10): 1111-1117).
HOME of Apoptopedia