Physiology of malate dehydrogenase and how dysregulation leads to disease.

Malate dehydrogenase (MDH) is pivotal in mammalian tissue metabolism, participating in various pathways beyond its classical roles and highlighting its adaptability to cellular demands. This enzyme is involved in maintaining redox balance, lipid synthesis, and glutamine metabolism and supports rapidly proliferating cells' energetic and biosynthetic needs. The involvement of MDH in glutamine metabolism underlines its significance in cell physiology.

Dopamine transporter membrane mobility is bidirectionally regulated by phosphorylation and palmitoylation.

The primary regulator of dopamine availability in the brain is the dopamine transporter (DAT), a plasma membrane protein that drives reuptake of released dopamine from the extracellular space into the presynaptic neuron. DAT activity is regulated by post-translational modifications that establish clearance capacity through impacts on transport kinetics, and dysregulation of these events may underlie dopaminergic imbalances in mood and psychiatric disorders. Here, using fluorescence recovery after photobleaching, we show that phosphorylation and palmitoylation induce opposing effects on DAT lateral membrane mobility, which may influence functional outcomes by regulating subcellular localization and binding partner interactions.

Inhibition of Tumor Microenvironment Cytokine Signaling Sensitizes Ovarian Cancer Cells to Antiestrogen Therapy.

Antiestrogen therapy (AET) is an alternative to cytotoxic chemotherapy for recurrent ovarian cancer, yet the often short duration of response suggests mechanisms of resistance. We previously demonstrated that tumor microenvironment interleukin-6/leukemia inhibitory factor (IL6/LIF) cytokines induce tumor cell JAK-STAT signaling to promote cancer growth. Crosstalk between estrogen signaling and cytokine signaling has been reported.

Sodium hydrogen exchanger (NHE1) palmitoylation and potential functional regulation.

Aims: Determine the effect of palmitoylation on the sodium hydrogen exchanger isoform 1 (NHE1), a member of the SLC9 family.

Main Methods: NHE1 expressed in native rat tissues or in heterologous cells was assessed for palmitoylation by acyl-biotinyl exchange (ABE) and metabolic labeling with [H]palmitate. Cellular palmitoylation was inhibited using 2-bromopalmitate (2BP) followed by determination of NHE1 palmitoylation status, intracellular pH, stress fiber formation, and cell migration.

Palmitoylation by Multiple DHHC Enzymes Enhances Dopamine Transporter Function and Stability.

The dopamine transporter (DAT) is a plasma membrane protein that mediates the reuptake of extracellular dopamine (DA) and controls the spatiotemporal dynamics of dopaminergic neurotransmission. The transporter is subject to fine control that tailors clearance of transmitter to physiological demands, and dysregulation of reuptake induced by psychostimulant drugs, transporter polymorphisms, and signaling defects may impact transmitter tone in disease states. We previously demonstrated that DAT undergoes complex regulation by palmitoylation, with acute inhibition of the modification leading to rapid reduction of transport activity and sustained inhibition of the modification leading to transporter degradation and reduced expression.

The DEK Oncoprotein Functions in Ovarian Cancer Growth and Survival.

DNA damage repair alterations play a critical role in ovarian cancer tumorigenesis. Mechanistic drivers of the DNA damage response consequently present opportunities for therapeutic targeting. The chromatin-binding DEK oncoprotein functions in DNA double-strand break repair.

Leukemia inhibitory factor functions in parallel with interleukin-6 to promote ovarian cancer growth.

Ovarian carcinoma-associated mesenchymal stem cells (CA-MSC) produce not only high levels of interleukin-6 (IL6) but also the related cytokine leukemia inhibitory factor (LIF). IL6-mediated activation of STAT3 is implicated as a critical therapeutic target for cancer therapy. Less is known about the role of LIF, which can similarly activate STAT3, in ovarian cancer.