Histone deacetylase 5 deacetylates the phosphatase PP2A for positively regulating NF-κB signaling.

ABSTRACT: Histone deacetylase 5 (HDAC5) has been reported to have a strong regulatory function in the proinflammatory response, but the mechanism is still unknown. Here, we identified HDAC5 as a positive regulator of NF-κB signaling in vivo. HDAC5-deficient mice exhibited enhanced survival in response to LPS challenge. Using LPS, TNFα, different kinds of viruses, hydrogen peroxide, or ultraviolet stimulation, we demonstrate that HDAC5-mediated regulation of NF-κB occurs in manners both dependent on and independent of IKK, an upstream kinase in the NF-κB signaling pathway. Deficiency in HDAC5 impaired the phosphorylation of IKKβ, subsequent phosphorylation of the NF-κB inhibitor protein IκBα and NF-κB subunit p65. We also show that the phosphatase PP2A repressed transcriptional activation of NF-κB by

SUBMITTER: Xu C 

PROVIDER: S-EPMC8634046 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature