期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 513, 期 4, 页码 947-951出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.04.077
关键词
HSP70; DNAJA3; Immune response; NF-kappa B; IKK beta/I kappa B alpha/NF-kappa B p65 complex
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [MEXT 16H05084, 24390014, 21117005, 21117001, 14657577]
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency
- Strategic International Cooperative program from Japan Science and Technology Agency
- Takeda Science Foundation
- Mitsubishi Foundation
- Astellas Foundation for Research on Metabolic Disorders
- Uehara Memorial Foundation
- Tokyo Biochemical Research Foundation
- Grants-in-Aid for Scientific Research [14657577, 21117005, 21117001] Funding Source: KAKEN
Nuclear factor kappa B (NF-kappa B) controls the transcription of various genes in response to immune stimuli. Our previous study revealed that the Droj2/DNAJA3 cochaperone contributes to the NF-kappa B pathway in Drosophila and humans. In general, the cochaperone is associated with the 70-kDa heat shock protein (HSP70) chaperone and the complex supports the folding of diverse target proteins. The cochaperone/chaperone functions in the NF-kappa B pathway, however, are not clearly understood. Here, we report that HSP70 proteins are involved in activating canonical NF-kappa B signaling during immune responses. In human cultured cells, HSP70 inhibitor destabilized the IKK beta/I kappa B alpha/NF-kappa B p65 complex and dampened the phosphorylation of NF-kappa B p65 in response to flagellin stimulation. We identified HSPA1A and HSPA8 as the HSP70 family proteins that physically interact with DNAJA3, and established their requirement for the phosphorylation of NF-kappa B p65. Furthermore, as in flies with knockdown of Droj2, flies with knockdown of Hsc70-4, a Drosophila homolog of HSPA8, were more susceptible to infection. Our results suggest that the chaperone/cochaperone complex regulates NF-kappa B immune signaling in an evolutionarily conserved manner. (C) 2019 Elsevier Inc. All rights reserved.
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