Regulation of keratin intermediate filaments by lysine acetylation

Abstract

Lysine acetylation and sumoylation are ubiquitous evolutionarily‐conserved posttranslational protein modifications that regulate important cellular functions, including cytoskeleton dynamics. Intermediate filaments are one of three major components of the cytoskeleton and are known to be extensively regulated at the posttranslational level. The aim of this study was to determine the role of lysine acetylation on the regulation of the cytoplasmic intermediate filament keratin 8 (K8). We used available proteomic data and site‐directed mutagenesis to identify Lys‐207 as a major acetylation site on human K8. Wild type K8 acetylation is increased in response to high glucose. The cytoplasmic deacetylase SIRT2 directly associates with K8 under low, but not high, glucose conditions. Analysis of liver tissues from mice with chronic liver injury induced by 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) show reciprocity of K8 acetylation and sumoylation. Our data demonstrate that keratin intermediate filaments are dynamically regulated by lysine acetylation and sumoylation in response to cellular energy status and tissue injury. This study was supported by NIH grants DK52951 (to M.B.O.) and DK93776 (to N.T.S).