Regulation of Sirtuin Function by Posttranslational Modifications

Regulation of Sirtuin Function by Posttranslational Modifications

Sirtuins are homologs of the yeast silencing information regulator 2 protein, an NAD(+)-dependent (histone) deacetylase. In mammals seven different sirtuins, SIRT1-7, have been identified, which share a common catalytic core domain but possess distinct N- and C-terminal extensions. This core domain elicits NAD(+)-dependent deacetylase and in some cases also ADP-ribosyltransferase, demalonylase,...

Induction of Posttranslational Modifications of Mitochondrial Proteins by ATP Contributes to Negative Regulation of Mitochondrial Function

It is generally accepted that ATP regulates mitochondrial function through the AMPK signaling pathway. However, the AMPK-independent pathway remains largely unknown. In this study, we investigated ATP surplus in the negative regulation of mitochondrial function with a focus on pyruvate dehydrogenase (PDH) phosphorylation and protein acetylation. PDH phosphorylation was induced by a high fat die...

Hierarchical CRMP2 posttranslational modifications control NaV1.7 function.

Voltage-gated sodium channels are crucial determinants of neuronal excitability and signaling. Trafficking of the voltage-gated sodium channel NaV1.7 is dysregulated in neuropathic pain. We identify a trafficking program for NaV1.7 driven by hierarchical interactions with posttranslationally modified versions of the binding partner collapsin response mediator protein 2 (CRMP2). The binding desc...

Spatiotemporal regulation of posttranslational modifications in the DNA damage response.

A timely and accurate cellular response to DNA damage requires tight regulation of the action of DNA damage response (DDR) proteins at lesions. A multitude of posttranslational modifications (PTMs) of chromatin and chromatin-associated proteins coordinates the recruitment of critical proteins that dictate the appropriate DNA repair pathway and enable the actual repair of lesions. Phosphorylatio...

Regulation of Ryanodine Receptor Ion Channels Through Posttranslational Modifications.