HSP70/DNAJA3 chaperone/cochaperone regulates NF-κB activity in immune responses

Kohei Kumada, Naoyuki Fuse, Tomomichi Tamura, Chisaki Okamori, Shoichiro Kurata

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


Nuclear factor kappa B (NF-κB) controls the transcription of various genes in response to immune stimuli. Our previous study revealed that the Droj2/DNAJA3 cochaperone contributes to the NF-κB 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-κB pathway, however, are not clearly understood. Here, we report that HSP70 proteins are involved in activating canonical NF-κB signaling during immune responses. In human cultured cells, HSP70 inhibitor destabilized the IKKβ/IκBα/NF-κB p65 complex and dampened the phosphorylation of NF-κB 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-κB 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-κB immune signaling in an evolutionarily conserved manner.

Original languageEnglish
Pages (from-to)947-951
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number4
Publication statusPublished - 2019 Jun 11


  • DNAJA3
  • HSP70
  • IKKβ/IκBα/NF-κB p65 complex
  • Immune response
  • NF-κB


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