首页|Histone deacetylase 4 inhibits NF-kB activation by facilitating IkBk sumoylation
Histone deacetylase 4 inhibits NF-kB activation by facilitating IkBk sumoylation
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NSTL
Protein modification by small ubiquitin-Uke modifier (SUMO) is an important regulatory mechanism for multiple cellular processes. Although the canonical pathway involving the ubiquitylation or phosphorylation of IkBoc has been well characterized, little is known about the sumoylation of IkBcx in the control of NF-kB activity. Here, we find that histone deacetylase 4 (HDAC4) negatively regulates tumor necrosis factor-alpha- or lipopolysaccharide-triggered NF-kB activation. HDAC4 belongs to the SUMO E3 ligase family and can directly sumoylate IkBoc. The cytoplasm location of HDAC4 is essential for IkBoc sumoylation. The Cys292 of HDAC4 is a key site for its SUMO E3 ligase activity. The sumoylation of IkBoc prevents its polyubiquitination and degradation because these two modifications occur both at the Lys21. Our findings reveal a previously undiscovered role for HDAC4 in the inflammatory response as a SUMO E3 ligase for kBa sumoylation. Our work provides insight into mechanisms ensuring optimal mediation of the NF-kB pathway.
NSTL
