biostudies-literatureSnider NTNIDDK NIH HHS241-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC3563689biostudies-literatureUnknown200(3)Lysine acetylation is an important posttranslational modification that regulates microtubules and microfilaments, but its effects on intermediate filament proteins (IFs) are unknown. We investigated the regulation of keratin 8 (K8), a type II simple epithelial IF, by lysine acetylation. K8 was basally acetylated and the highly conserved Lys-207 was a major acetylation site. K8 acetylation regulated filament organization and decreased keratin solubility. Acetylation of K8 was rapidly responsive to changes in glucose levels and was up-regulated in response to nicotinamide adenine dinucleotide (NAD) depletion and in diabetic mouse and human livers. The NAD-dependent deacetylase sirtuin 2 (SIRT2) associated with and deacetylated K8. Pharmacologic or genetic inhibition of SIRT2 decreased K8 solThe Journal of cell biologyGlucose and SIRT2 reciprocally mediate the regulation of keratin 8 by lysine acetylation.PMC3563689P30 DK34933K01 DK093776P30 DK034933R01 DK52951R01 DK052951Omary MBSnider NTGriggs NWRui LKwan RLeonard JMfalseGlucose and SIRT2 reciprocally mediate the regulation of keratin 8 by lysine acetylation.Lysine acetylation is an important posttranslational modification that regulates microtubules and microfilaments, but its effects on intermediate filament proteins (IFs) are unknown. We investigated the regulation of keratin 8 (K8), a type II simple epithelial IF, by lysine acetylation. K8 was basally acetylated and the highly conserved Lys-207 was a major acetylation site. K8 acetylation regulated filament organization and decreased keratin solubility. Acetylation of K8 was rapidly responsive to changes in glucose levels and was up-regulated in response to nicotinamide adenine dinucleotide (NAD) depletion and in diabetic mouse and human livers. The NAD-dependent deacetylase sirtuin 2 (SIRT2) associated with and deacetylated K8. Pharmacologic or genetic inhibition of SIRT2 decreased K8 sol2013-01-01T00:00:00Z2013 Feb2025-05-18T11:57:45.896Z2025-05-18T11:57:45.896ZS-EPMC35636892335824410.1083/jcb.201209028