Karger AG, Basel
Background/Aims: MicroRNAs (miRNAs) play selleckchem SB203580 an important role in cellular differentiation and cancer pathogenesis. However, their role in promoting the malignant phenotype of myeloproliferative diseases and their importance for differential diagnosis of early-stage chronic myeloproliferative diseases (CMPDs) remains widely obscure. Methods: In this study, we systematically evaluated the differential expression of miRNAs previously described to be associated with myelopoiesis and myeloproliferative pathogenesis by quantitative RT-PCR in polycythemia vera, essential thrombocythemia, early primary myelofibrosis (PMF) and normal hematopoiesis. Our goal was to establish certain miRNAs as potential markers for CMPDs to facilitate the differentiation between these diseases and to further investigate molecular differences between the subtypes of myeloproliferative neoplasia.

Results: An aberrant expression of miRNAs 10a and 150 could be demonstrated for essential thrombocythemia and PMF as well as for polycythemia vera and PMF, respectively. The expression of miR-150 could further be shown to correlate with both JAK2 allele burden and peripheral blood counts. Conclusion: Thus, the miRNAs investigated in this study seem to be potential marker oncomiRs in the differential diagnosis of CMPDs and possibly hold potential for the elucidation of a JAK2-independent mechanism of pathogenesis. Copyright (c) 2013 S. Karger AG, Basel
Allostery is a fundamental regulatory mechanism that is based on a functional modulation of a site by a distant site.

Allosteric regulation can be triggered by binding of diverse allosteric effectors, ranging from small molecules to macromolecules, and is therefore offering promising opportunities for functional modulation in a wide range of applications including the development of chemical probes or drug discovery. Here, we provide an overview of key classes of allosteric protease effectors, their corresponding molecular mechanisms, and their practical implications.
Small-molecule modulation of protein-protein interactions (PPIs) is one of the most exciting but also difficult fields in chemical biology and drug development. As one of the most important “hub” proteins with at least 200-300 interaction partners, the 14-3-3 proteins are an especially fruitful case for PPI intervention.

Here, we summarize recent success stories in small Anacetrapib molecule modulation, both inhibition and stabilization, of 14-3-3 PPIs. The chemical breath of modulators includes natural products such as fusicoccin A and derivatives but also compounds identified via high throughput and in silica screening, which has yielded a toolbox of useful inhibitors and stabilizers for this interesting class of adapter proteins. Protein-protein interactions selleck (PPIs) are involved in almost all biological processes, with any given protein typically engaged in complexes with other proteins for the majority of its lifetime.