Glucose and SIRT2 reciprocally mediate the regulation of keratin 8 by lysine acetylation

Natasha T. Snider, Jessica M. Leonard, Raymond Kwan, Nicholas W. Griggs, Liangyou Rui, M. Bishr Omary

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Lysine acetylation is an important posttranslational modi-fication that regulates microtubules and microfila-ments, but its effects on intermediate filament proteins (IFs) are unknown. We investigated the regulation of kera-tin 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 fila-ment organization and decreased keratin solubility. Acety-lation 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. Pharmaco-logic 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 mod-ulating keratin phosphorylation.

Original languageEnglish (US)
Pages (from-to)241-247
Number of pages7
JournalJournal of Cell Biology
Issue number3
StatePublished - Feb 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology


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