Signaling Pathways For Translation

This volume presents the response of the eukaryotic translational apparatus to cellular stress and apoptosis, including kinases activated through both the ERK and stress-activated pathways. It further explores two agents that inhibit protein synthesis, calcium and the immunosuppressant rapamycin. Six chapters written by leading experts in the field provide both new data and comprehensive literature reviews. Both the regulation of initiation and elongation are discussed, and the mechanisms of apoptosis are related to changes in the protein synthesis machinery.

The articles in the present volume are by major contributors to our under standing of signaling pathways affecting protein synthesis. They focus pri marily on two extracellular anabolic signals, although others are included as well. Insulin is one of the best-studied extracellular regulators of protein syn thesis. Several of the known pathways for regulation of protein synthesis were elucidated using insulin-dependent systems. Regulation of protein synthesis by amino acids, by contrast, is an emerging field that has recently received a great deal of attention. The dual role of amino acids as substrates for protein syn thesis and regulators of the overall process has only recently been recognized. Since amino acids serve as precursors for proteins, one might expect that with holding an essential amino acid would inhibit the elongation phase. Surpris ingly, research has shown that it is the initiation phase of protein synthesis that is restricted during amino acid starvation. Understanding the mechanisms by which the biosynthesis of proteins is reg ulated is important for several reasons. Protein synthesis consumes a major portion of the cellular ATP that is generated. Therefore, small changes in protein synthesis can have great consequences for cellular energy metabolism. Translation is also a major site for control of gene expression, since messenger RNAs differ widely in translational efficiency, and changes to the protein syn thesis machinery can differentially affect recruitment of individual mRNAs.

The NMDA receptor plays a critical role in the development of the central nervous system and in adult neuroplasticity, learning, and memory. Therefore, it is not surprising that this receptor has been widely studied. However, despite the importance of rhythms for the sustenance of life, this aspect of NMDAR function remains poorly studied. Written

Protein synthesis is a fundamental aspect of gene expression across kingdoms. The regulation of translation is important for many biological processes including cell fate determination, development, and growth and is especially crucial to maintain cellular homeostasis during cellular stress and virus infection. Misregulation of protein translation can contribute to diseases such as diabetes, cancer, and neurodegenerative diseases. In this chapter, we highlight the basic understanding of eukaryotic translation and the major regulations that control biological events. We focus on signaling pathways that regulate overall protein synthesis and also mechanisms that control translation of specific mRNAs such as cis-acting elements within the 5' and 3 untranslated regions (UTR). Understanding these mechanisms provide insights into the fundamental gene regulations that may provide new targets for combating disease and virus infections.

This book, for the first time, comprehensively assembles and analyzes a large body of information on the role of the fundamental mechanism of the protein biosynthesis pathway, translation, in cancer biology. It systematically explores the function of the translation machinery and its regulation, including cell signaling, in the development, maintenance and progression of human cancer. The work presented here unveils the tremendous potential and applications of this vast and exciting branch of genetic, biochemical and molecular science in cancer medicine and drug development. Chapters contributed by experts in the field take the reader on a journey that starts with a dissection of the translation machinery and its regulation in norm and cancer. Later chapters characterize etiological and pathogenetic roles that translation plays in specific cancer types. Various aspects of diagnostic, prognostic and therapeutic significance of the translation machinery and its control in cancer are discussed. Readers will discover the importance of the process of translation and its regulatory mechanisms in physiology and cancer biology. The chapters and the numerous illustrations included here were contributed by expert scientists and clinicians from renowned academic and clinical establishments in Canada, the United States of America, the United Kingdom, Italy, France, Belgium, Spain, Germany and Australia. The book conveys information and knowledge that may interest a broad range of students and scholars ranging from basic scientists to clinicians and drug developers seeking to better understand the protein synthesis and its aberrations in cancer biology and cancer medicine.

The synthesis of proteins by ribosomes is a fundamental cellular process. Cells must tightly control protein synthesis to maintain homeostasis and regulate proliferation, growth, differentiation, and development. Indeed, aberrant translational control is associated with cancer, several neurologic syndromes, and genetic disorders including "ribosomopathies." Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers our current understanding of protein synthesis and its control, from the genomic level to single- molecule analysis and single-cell imaging. The contributors describe the fundamental steps in protein synthesis (initiation, elongation, and termination), the factors involved, and high- resolution structures of the translational machinery. They review the targets of translational control (e.g., initiation factors and mRNAs) and how signaling pathways modulate this machinery. The roles of the endoplasmic reticulum, the unfolded protein response, processing bodies (P-bodies), stress granules, and small RNAs (including microRNAs) are also covered. This volume includes discussion of translational deregulation in cancer and the development of therapeutic agents that target translation initiation. Thus, it is an essential reference for cell and molecular biologists, as well as developmental and neurobiologists, oncologists, virologists, and all those investigating human diseases associated with translation dysfunction.

Signaling Pathways in Liver Diseases, 2nd edition focuses on signaling pathways which are particularly important in liver diseases. Recent progress brought hepatology to new frontiers. The increasing frequency of surgery on steatotic and cirrhotic liver obliges liver surgeons and hepatologists to understand the molecular mechanisms at play in these situations and how they can be influenced. Better comprehension of the cellular mechanisms participating in liver regeneration, hepato-cellular apoptosis and ischemia/reperfusion inquiry is mirrored by a dramatic increase in complexity. The number and scope of publications is intimidating and difficult for busy individuals to extract a coherent framework. This book will serve as a source of information facilitating the reading of the literature and the planning of trials. Translational medicine implies knowledge of the molecular targets for novel therapeutic strategies. It will furthermore stimulate more research and lead to better exchange between the laboratory, the clinical ward and the operation room.