Linking Phosphoinositides to Proteins: A Novel Signaling PIPeline.

Phosphoinositide (PIP) signaling plays pivotal roles in myriad biological processes and is altered in many diseases including cancer. Canonical PIP signaling involves membrane-associated PIP lipid second messengers that modulate protein recruitment and activity at membrane focal points. In the nucleus, PIP signaling operates separately from membranous compartments defining the paradigm of non-canonical PIP signaling.

Aryl Hydrocarbon Receptor Knockout Accelerates PanIN Formation and Fibro-Inflammation in a Mutant Kras -Driven Pancreatic Cancer Model.

Objectives: The pathogenesis of pancreas cancer (PDAC) remains poorly understood, hindering efforts to develop a more effective therapy for PDAC. Recent discoveries show the aryl hydrocarbon receptor (AHR) plays a crucial role in the development of several cancers and can be targeted for therapeutic effect. However, its involvement in the pathogenesis of PDAC remains unclear.

Environmental pollutants and phosphoinositide signaling in autoimmunity.

Environmental pollution stands as one of the most critical challenges affecting human health, with an estimated mortality rate linked to pollution-induced non-communicable diseases projected to range from 20% to 25%. These pollutants not only disrupt immune responses but can also trigger immunotoxicity. Phosphoinositide signaling, a pivotal regulator of immune responses, plays a central role in the development of autoimmune diseases and exhibits high sensitivity to environmental stressors.

Heme biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue.

With age, people tend to accumulate body fat and reduce energy expenditure . Brown (BAT) and beige adipose tissue dissipate heat and increase energy expenditure via the activity of the uncoupling protein UCP1 and other thermogenic futile cycles . The activity of brown and beige depots inversely correlates with BMI and age , suggesting that promoting thermogenesis may be an effective approach for combating age-related metabolic disease .

Regulation of NRF2 by Phosphoinositides and Small Heat Shock Proteins.

Unlabelled: Reactive oxygen species (ROS) are generated by aerobic metabolism, and their deleterious effects are buffered by the cellular antioxidant response, which prevents oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) is a master transcriptional regulator of the antioxidant response. Basal levels of NRF2 are kept low by ubiquitin-dependent degradation of NRF2 by E3 ligases, including the Kelch-like ECH-associated protein 1 (KEAP1).

Lipid transfer proteins and a PI 4-kinase initiate nuclear phosphoinositide signaling.

Unlabelled: Phosphoinositide (PIP ) messengers are present in non-membranous regions of nuclei, where they are assembled into a phosphatidylinositol (PI) 3-kinase (PI3K)/Akt pathway that is distinct from the cytosolic membrane-localized pathway. In the nuclear pathway, PI kinases/phosphatases bind the p53 tumor suppressor protein (wild-type and mutant) to generate p53-PIP complexes that regulate Akt activation. However, this pathway is dependent on poorly characterized nuclear PIP pools.

Aryl hydrocarbon receptor knockout accelerates PanIN formation and fibro-inflammation in a mutant -driven pancreatic cancer model.

Objectives: The pathogenesis of pancreas cancer (PDAC) remains poorly understood, hindering efforts to develop a more effective therapy for PDAC. Recent discoveries show the aryl hydrocarbon receptor (AHR) plays a crucial role in the pathogenesis of several cancers, and can be targeted for therapeutic effect. However, its involvement in PDAC remains unclear.

Chronic jetlag-induced alterations in pancreatic diurnal gene expression.

Cell-autonomous circadian clocks exist in nearly every organ and function to maintain homeostasis through a complex series of transcriptional-translational feedback loops. The response of these peripheral clocks to external perturbations, such as chronic jetlag and shift work, has been extensively investigated. However, an evaluation of the effects of chronic jetlag on the mouse pancreatic transcriptome is still lacking.