Activation of the NF-κB pathway by Caspase 8 and its homologs
- 14 September 2000
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 19 (39), 4451-4460
- https://doi.org/10.1038/sj.onc.1203812
Abstract
Caspase 8 is the most proximal caspase in the caspase cascade and has been known for its role in the mediation of cell death by various death receptors belonging to the TNFR family. We have discovered that Caspase 8 can activate the NF-kappaB pathway independent of its activity as a pro-apoptotic protease. This property is localized to its N-terminal prodomain, which contains two homologous death effector domains (DEDs). Caspase 10 and MRIT, two DEDs-containing homologs of Caspase 8, can similarly activate the NF-kappaB pathway. Dominant-negative mutants of the Caspase 8 prodomain can block NF-kappaB induced by Caspase 8, FADD and several death receptors belonging to the TNFR family. Caspase 8 can interact with multiple proteins known to be involved in the activation of the NF-kappaB pathway, including the serine-threonine kinases RIP, NIK, IKK1 and IKK2. Thus, DEDs-containing caspases and caspase homolog(s) may have functions beyond their known role in the mediation of cell death. Oncogene (2000) 19, 4451 - 4460.Keywords
This publication has 43 references indexed in Scilit:
- IEX -1L, an Apoptosis Inhibitor Involved in NF-κB-Mediated Cell SurvivalScience, 1998
- Suppression of Steady-state, but not Stimulus-induced NF-κB Activity Inhibits Alphavirus-induced ApoptosisThe Journal of cell biology, 1998
- The IκB Kinase Complex (IKK) Contains Two Kinase Subunits, IKKα and IKKβ, Necessary for IκB Phosphorylation and NF-κB ActivationCell, 1997
- Identification and Characterization of an IκB KinaseCell, 1997
- MAP3K-related kinase involved in NF-KB induction by TNF, CD95 and IL-1Nature, 1997
- Dissection of TNF Receptor 1 Effector Functions: JNK Activation Is Not Linked to Apoptosis While NF-κB Activation Prevents Cell DeathCell, 1996
- FLICE, A Novel FADD-Homologous ICE/CED-3–like Protease, Is Recruited to the CD95 (Fas/APO-1) Death-Inducing Signaling ComplexCell, 1996
- Involvement of MACH, a Novel MORT1/FADD-Interacting Protease, in Fas/APO-1- and TNF Receptor–Induced Cell DeathCell, 1996
- Correction of Radiation Sensitivity in Ataxia Telangiectasia Cells by a Truncated IκB-αScience, 1995
- FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosisCell, 1995