SIRT1: a novel regulator in colorectal cancer.

The class-III histone deacetylase SIRT1 is the most extensively investigated sirtuin deacetylase. It is resistant to the broad deacetylase inhibitor trichostatin A and depends on oxidized nicotinamide adenine nucleotide (NAD). SIRT1 plays a crucial role in the tumorigenesis of numerous types of cancers, including colorectal cancer (CRC).

The role of de novo protein synthesis and SIRT1 in ER stress-induced Atf4 and Chop mRNA expression in mammalian cells.

Endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR) have been implicated in the pathogenesis of many common human diseases. Integral to the UPR and an important determinant in cell fate is the expression of the pro-apoptotic transcription factor C/EBP homologous protein (CHOP). This is promoted by activating transcription factor 4 (ATF4) whose expression is rapidly up-regulated in response to ER stress through an eIF2α phosphorylation-dependent increase in protein synthesis.

Exendin-4 stimulates islet cell replication via the IGF1 receptor activation of mTORC1/S6K1.

Glucagon-like peptide 1 receptor (GLP1R) agonists, such as exendin-4, potentiate glucose-stimulated insulin secretion and are currently used in the management of type 2 diabetes. Interestingly, GLP1R agonists also have the ability to augment β-cell mass. In this report, we provide evidence that in the presence of glucose, exendin-4 stimulates rodent islet cell DNA replication via the activation of ribosomal protein S6 kinase 1 (S6K1) and that this is mediated by the protein kinase B (PKB)-dependent activation of mTOR complex 1 (mTORC1).