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The high-mobility-group (HMG) box is a conserved DNA-binding domain found in a family of transcription factors that regulate growth and development. One family member, Ste11p, directs sexual differentiation of Schizosaccharomyces pombe by binding specific DNA sequences upstream of genes required for mating and meiosis. Here, we show that Ste11p is a shuttling protein. In growing cells, Ste11p is present in low levels and is pancellular. Mating pheromones and nutrient limitation trigger nuclear accumulation and increased expression of the transcription factor. Several mechanisms likely control Ste11p localization. First, the 14-3-3 protein, Rad24p, binds phosphorylated Ste11p and inhibits its nuclear accumulation. Second, the HMG domain of Ste11p contains a basic cluster nuclear localization signal. Finally, treatment of cells with leptomycin B, an exportin inhibitor, results in the nuclear accumulation of Ste11p. A Ste11p deletion mutation, ⌬C54, mimics the effects of leptomycin B. The C54 region contains no identifiable nuclear export signal but instead is required for biological activity and to stimulate Ste11p target gene expression. These results provide evidence that both nuclear import and export mechanisms operate to regulate cellular localization of an HMG box protein. In addition, they establish a paradigm for the potential role of pheromone/hormone-like polypeptides in cellular localization of this important class of developmental regulators.

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Galanin is present in normal and tumorous human pituitaries. In addition, GAL colocalizes exclusively in corticotrophs of normal pituitaries and is coexpressed almost exclusively in corticotrophs from functioning and nonfunctioning tumours. The finding that corticotroph adenomas can function irrespective of the presence of GAL suggests that GAL may not play a pathophysiological role in Cushing's disease. However, the better surgical outcome observed in patients with Cushing's disease who had tumours positive for GAL-IR suggests that the expression of GAL confers a less aggressive tumour phenotype.

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H yperlipidemia is observed in 40% to 60% of organ transplant recipients and has been linked to the use of immunosuppressant agents such as corticosteroids, sirolimus, and cyclosporine A (CsA).1-3 Transplant hyperlipidemia is characterized by high plasma cholesterol and triglyceride levels. Specifically, CsA increases very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) concentrations and shows variable effects on plasma high-density lipoprotein. Although multiple factors potentially contribute to hyperlipidemia in patients, such as post-transplantation obesity, multiple drug therapy, and diabetes mellitus, CsA monotherapy can independently lead to elevated plasma triglyceride and cholesterol levels in humans which are reversible on cessation of immunosuppression therapy. 4 The immunosuppressive effect of CsA is mediated by inhibition of protein phosphatase 2B (calcineurin) and subsequent activation of the transcription factor nuclear factor of transcription. The mechanism(s) by which CsA leads to hyperlipidemia © 2016 American Heart Association, Inc.