Biology subjects

Kawase, Y.

Publications and source records attributed to Kawase, Y..

2 recordsLinked to original sources

bioRxiv2024

Nobiletin, a Polymethoxyflavonoid, Activates the Desuccinylase Activity of SIRT5 and Prevents the Development of Heart Failure

Nobiletin is a natural compound useful for the prevention and treatment of several diseases. However, the precise role of nobiletin in heart failure is unclear. Nobiletin treatment prevents pressure overload- and myocardial infarction-induced heart failure. Using affinity purification of biotinylated nobiletin from rat heart cell lysates, we identified sirtuin 5 (SIRT5) as a novel nobiletin-binding protein. Nobiletin enhanced the desuccinylase activity of SIRT5 in vitro. Compared to wild-type mice, SIRT5-overexpressing transgenic mice resisted pressure overload-induced systolic dysfunction. Conversely, SIRT5 knockout disrupted the nobiletin-mediated therapeutic effects on heart failure in mice. SIRT5 desuccinylated p300 at lysine 1568 and reduced the histone acetyltransferase (HAT) activity of p300. The desuccinylated p300 mutant suppressed the phenylephrine-induced cardiomyocyte hypertrophic responses. These findings suggest that nobiletin prevents heart failure development through SIRT5-dependent inhibition of p300-HAT activity. Nobiletin, a nontoxic dietary compound, is a potential therapeutic agent for heart failure in humans.

molecular biology↗

bioRxiv2020

Importin α2 associates with chromatin via a novel DNA binding domain

Nuclear transport of proteins is important for facilitating appropriate nuclear functions. The proteins of the importin family play key roles in nuclear transport as transport receptors for a huge number of nuclear proteins. Additionally, these proteins possess other functions, including chromatin association and gene regulation. However, these non-transport functions of importin are not yet fully understood, especially their molecular-level mechanisms for functioning with chromatin and their consequences. Here, we report the novel molecular characteristics of importin involving binding to diverse sequences in chromatin. We newly identified and characterized a DNA-binding domain--the Nucleic Acid Associating Trolley pole domain (NAAT domain)--in the N-terminal region of importin within the conventional importin {beta} binding (IBB) domain, which was shown to be necessary for nuclear transport of cargo proteins. We propose a stroll and locate model to explain the association of importin with chromatin. This is the first study to delineate the interaction between importin and chromatin DNA via the NAAT domain, indicating the bifunctionality of the importin N-terminal region for nuclear transport and chromatin association.

molecular biology↗