| First Author | Snider NT | Year | 2013 |
| Journal | J Cell Biol | Volume | 200 |
| Issue | 3 | Pages | 241-7 |
| PubMed ID | 23358244 | Mgi Jnum | J:195217 |
| Mgi Id | MGI:5476875 | Doi | 10.1083/jcb.201209028 |
| Citation | Snider NT, et al. (2013) Glucose and SIRT2 reciprocally mediate the regulation of keratin 8 by lysine acetylation. J Cell Biol 200(3):241-7 |
| abstractText | 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 solubility and affected filament organization. Inhibition of K8 Lys-207 acetylation resulted in site-specific phosphorylation changes of K8. Therefore, K8 acetylation at Lys-207, a highly conserved residue among type II keratins and other IFs, is up-regulated upon hyperglycemia and down-regulated by SIRT2. Keratin acetylation provides a new mechanism to regulate keratin filaments, possibly via modulating keratin phosphorylation. |
