IL-3 and oncogenic Abl regulate the myeloblast transcriptome by altering mRNA stability

The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth through autocrine or paracrine mechanisms. The degree to which IL-3 acts at the posttranscriptional level is largely unknown. We have conducted global mRNA decay profiling and bioinformatic analyses in 32Dcl3 myeloblasts indicating that IL-3 caused immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Stabilized transcripts were enriched for AU-Response elements (AREs), and an ARE-containing domain from the interleukin-6 (IL-6) 3′-UTR rendered a heterologous gene responsive to IL-3-mediated transcript stabilization. Many IL-3-stabilized transcripts had been associated with leukemic transformation. Deregulated Abl kinase shared with IL-3 the ability to delay turnover of transcripts involved in proliferation or differentiation blockade, relying, in part, on signaling through the Mek/ Erk pathway. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of an mRNA network linked to IL-3 contributes to leukemic cell growth. © 2009 Ernst et al

Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements

A considerable number of genes that code for AU-rich mRNAs including cytokines, growth factors, transcriptional factors, and certain receptors are involved in both chronic inflammation and cancer. Overexpression of these genes is affected by aberrations or by prolonged activation of several signaling pathways. AU-rich elements (ARE) are important cis-acting short sequences in the 3′UTR that mediate recognition of an array of RNA-binding proteins and affect mRNA stability and translation. This review addresses the cellular and molecular mechanisms that are common between inflammation and cancer and that also govern ARE-mediated post-transcriptional control. The first part examines the role of the ARE-genes in inflammation and cancer and sequence characteristics of AU-rich elements. The second part addresses the common signaling pathways in inflammation and cancer that regulate the ARE-mediated pathways and how their deregulations affect ARE-gene regulation and disease outcome

An expanding culture of control? The municipal administrative sanctions Act in Belgium

This article provides an in-depth study of the Act on Municipal Administrative Sanctions 1999 (MAS), which is the first major piece of legislation regulating antisocial behaviour in Belgium. MAS provides municipalities with an instrument to sanction antisocial behaviour and conduct perceived to disturb public order. The article uses Garland’s(2001) thesisonthecultureofcontroltoanalysewhetherMAShasledtoincreasedgovernmentcontrol and the exclusion of significant groups of the population. The research is based on a multiple case study in which the application of MAS was analysed over a 25-year period of security policies in Belgium (1985–2010). The Act’s implementation was studied in the two Belgian cities of Antwerp and Liège in order to consider the influence of the Flemish government and the Walloon government, respectively, in this policy area. The article uses insights from this comparison to revisit the culture of control thesis and its limitations in understanding the political competition that exists over the formulation of policies on antisocial behaviour. Effective Protection of Fundamental Rights in a pluralist worl