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Protein phosphatase X interacts with c-Rel and stimulates c-Rel/nuclear factor kappaB activity
M C Hu1, Q Tang-Oxley, W R Qiu
1Department of Cell Biology, Amgen, Inc., Thousand Oaks, California 91320, USA.
Abstract:
Nuclear factor kappaB (NF-kappaB) and the Rel family of proteins are pleiotropic transcription factors that play central roles in the immune and inflammatory responses, as well as apoptosis. Here, we identified a serine/threonine protein phosphatase X (PPX; also called protein phosphatase 4 (PP4)) that specifically associated with c-Rel, NF-kappaB p50, and RelA. The amino acid sequences of human and mouse PPX are 100% identical, and the PPX gene was mapped to human chromosome 16 p11.2. Overexpression of PPX, but not catalytically inactive PPX mutants, stimulated the DNA-binding activity of c-Rel and activated NF-kappaB-mediated transcription. These results suggest that PPX is a novel activator of c-Rel/NF-kappaB.
Insights
Protein phosphatase X (PPX) activates the Nuclear factor kappaB (NF-kappaB) pathway. This phosphatase specifically associates with c-Rel, NF-kappaB p50, and RelA, enhancing immune and inflammatory responses.
Area of Science:
- Molecular Biology
- Immunology
- Cell Signaling
Background:
- Nuclear factor kappaB (NF-kappaB) and Rel proteins are key transcription factors in immune and inflammatory processes.
- Understanding regulators of NF-kappaB is crucial for modulating immune responses.
Purpose of the Study:
- To identify novel regulators of the NF-kappaB pathway.
- To investigate the role of protein phosphatase X (PPX) in NF-kappaB signaling.
Main Methods:
- Co-immunoprecipitation to identify interacting proteins.
- Gene mapping to determine chromosomal location.
- Overexpression studies with wild-type and mutant PPX to assess functional impact on NF-kappaB activity.
Main Results:
- Protein phosphatase X (PPX) was identified as a binding partner for c-Rel, NF-kappaB p50, and RelA.
- Human and mouse PPX sequences are identical; the PPX gene is located on chromosome 16p11.2.
- Overexpression of active PPX, but not inactive mutants, enhanced c-Rel DNA-binding and NF-kappaB-mediated transcription.
Conclusions:
- Protein phosphatase X (PPX) is a novel activator of the c-Rel/NF-kappaB signaling pathway.
- PPX's phosphatase activity is essential for its role in activating NF-kappaB.