Death and decoy receptors and p53-mediated apoptosis.
Recently, several tumor necrosis factor receptor 1 (TNF-R1) and Fas-related death receptors have been discovered and include DR3, DR4, DR5 and DR6. These receptors contain an extracellular region containing varying numbers of cysteine-rich domains and an intracellular region that contains the death domain. The death receptors are activated in a ligand-dependent or independent manner and transduce apoptotic signals via their respective intracellular death domains. In addition to death receptors, several decoy molecules have also been identified and include DcR1/TRID, DcR2/TRUNDD, DcR3 and osteoprotegrin (OPG). The decoy molecules do not transduce apoptotic signals but rather compete with the death receptors for ligand binding and thereby inhibit ligand-induced apoptosis. Recent evidence suggests that p53 upregulates the expression of death receptors Fas and DR5, and thus, may mediate apoptosis in part via Fas and/or DR5. However, p53 also regulates the expression of TRAIL decoy receptors DcR1/TRID and DR2/TRUNDD. Although the significance of p53-dependent regulation of decoy receptors remains unclear, evidence suggests that DcR1/TRUNDD appears to inhibit 53-mediated apoptosis. It is, therefore, possible that p53 may blunt its DR5-dependent apoptotic effects by controlling the levels of decoy receptors.
Sheikh
M S
MS
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
Fornace
A J
AJ
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D016159:Tumor Suppressor Protein p53