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The death effector domain protein family: regulators of cellular homeostasis
Michael D Tibbetts1, Lixin Zheng, Michael J Lenardo
1Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract:
The death effector domain (DED) occurs in proteins that regulate programmed cell death. Both pro- and anti-apoptotic proteins containing DEDs have been identified. For Fas and possibly other death receptors, homotypic DED interactions connect the Fas-associated death domain (FADD) protein to caspase-8 and caspase-10 to mediate formation of the death-inducing signal complex. This complex can be inhibited by other DED-containing proteins. Accumulating evidence now suggests that DED-containing proteins have additional roles in controlling pathways of cellular activation and proliferation. Thus, the DED defines a family of proteins that may be pivotal to cellular homeostasis by establishing a 'cell renewal set point' that coregulates proliferation and apoptosis in parallel.
Insights
Death effector domain (DED) proteins regulate cell death and proliferation. These DED proteins are pivotal to cellular homeostasis, controlling cell renewal set points by balancing apoptosis and cell growth.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Death effector domains (DEDs) are protein interaction modules found in proteins regulating programmed cell death.
- Both pro-apoptotic and anti-apoptotic proteins contain DEDs.
- DEDs mediate interactions in signaling complexes like the death-inducing signal complex (DISC).
Purpose of the Study:
- To explore the broader roles of DED-containing proteins beyond apoptosis.
- To investigate the involvement of DED proteins in cellular activation and proliferation pathways.
- To establish the DED as a protein family critical for cellular homeostasis.
Main Methods:
- Literature review and analysis of existing research on DED proteins.
- Examination of protein interaction data involving DEDs.
- Functional analysis of DED-containing proteins in cell death and proliferation pathways.
Main Results:
- DED proteins are involved in both pro-apoptotic and anti-apoptotic functions.
- Homotypic DED interactions are crucial for DISC formation, involving FADD, caspase-8, and caspase-10.
- DED-containing proteins can inhibit DISC formation.
- Emerging evidence indicates DED proteins also regulate cellular activation and proliferation.
Conclusions:
- The DED defines a protein family with critical roles in cellular homeostasis.
- DED proteins establish a 'cell renewal set point' that co-regulates apoptosis and proliferation.
- Understanding DED protein functions is key to comprehending the balance between cell death and growth.