Epigenetic Activation of a Subset of mRNAs by eIF4E Explains Its Effects on Cell Proliferation

BACKGROUND: Translation deregulation is an important mechanism that causes aberrant cell growth, proliferation and survival. eIF4E, the mRNA 5′ cap-binding protein, plays a major role in translational control. To understand how eIF4E affects cell proliferation and survival, we studied mRNA targets that are translationally responsive to eIF4E. METHODOLOGY/PRINCIPAL FINDINGS: Microarray analysis of polysomal mRNA from an eIF4E-inducible NIH 3T3 cell line was performed. Inducible expression of eIF4E resulted in increased translation of defined sets of mRNAs. Many of the mRNAs are novel targets, including those that encode large- and small-subunit ribosomal proteins and cell growth-related factors. In addition, there was augmented translation of mRNAs encoding anti-apoptotic proteins, which conferred resistance to endoplasmic reticulum-mediated apoptosis. CONCLUSIONS/SIGNIFICANCE: Our results shed new light on the mechanisms by which eIF4E prevents apoptosis and transforms cells. Downregulation of eIF4E and its downstream targets is a potential therapeutic option for the development of novel anti-cancer drugs

Proline Metabolism and Its Functions in Development and Stress Tolerance

Proline takes an exceptional place among the proteinogenic amino acids by its specific accumulation in pollen and in response to multiple types of stress. Despite the more than 50 years of research, the biochemical pathways of proline biosynthesis and degradation still await their complete characterization in plants. Also, the molecular and physiological functions of proline metabolism in plant development and defense against stress are not yet fully understood. This chapter focuses on the current knowledge about the biochemical pathways of proline metabolism in plants, on its tissue-specific regulation and subcellular compartmentation, and on still open questions. Furthermore, we will summarize what is known about the influence of proline metabolism on plant development under optimal growth conditions and how it may support continued development despite the impact of stress. The cognate chapter “Regulation of Proline Accumulation and its molecular and physiological Functions in Stress Defense” will focus on the possible beneficial functions of proline metabolism and accumulation in the defense response against diverse stresses. With these two cohesive chapters, we aim to provide a comprehensive picture of the current knowledge and the open research questions in proline-dependent stress defense