Nature Immunology 8, 584 - 591 (2007)
Published online: 29 April 2007 | doi:10.1038/ni1464
PDLIM2-mediated termination of transcription factor NF-B activation by intranuclear sequestration and degradation of the p65 subunit
Activation of transcription factor NF-B in the innate immune system is tightly regulated to prevent excessive inflammatory responses. How NF-B activation is terminated, however, is not fully understood. Here we report that PDLIM2 negatively regulated NF-B activity, acting as a nuclear ubiquitin E3 ligase targeting the p65 subunit of NF-B. PDLIM2 bound to p65 and promoted p65 polyubiquitination. In addition, PDLIM2 targeted p65 to discrete intranuclear compartments where polyubiquitinated p65 was degraded by the proteasome. PDLIM2 deficiency resulted in larger amounts of nuclear p65, defective p65 ubiquitination and augmented production of proinflammatory cytokines in response to innate stimuli. Our findings delineate a pathway by which PDLIM2 terminates NF-B activation through intranuclear sequestration and subsequent degradation.
- Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
- Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
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