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Author:
Publisher: Academic Press
ISBN: 9780123739698
Category : Science
Languages : en
Pages : 512
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Book Description
For over fifty years the Methods in Enzymology series has been the critically aclaimed laboratory standard and one of the most respected publications in the field of biochemistry. The highly relevant material makes it an essential publication for researchers in all fields of life and related sciences. This volume, the second of three on the topic of Translation Initiation includes articles written by leaders in the field.
Author:
Publisher: Academic Press
ISBN: 9780123739698
Category : Science
Languages : en
Pages : 512
Get Book Here
Book Description
For over fifty years the Methods in Enzymology series has been the critically aclaimed laboratory standard and one of the most respected publications in the field of biochemistry. The highly relevant material makes it an essential publication for researchers in all fields of life and related sciences. This volume, the second of three on the topic of Translation Initiation includes articles written by leaders in the field.
Author: Greco Hernández
Publisher: Springer
ISBN: 3319394681
Category : Science
Languages : en
Pages : 564
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Book Description
The “omics” era has given a new perspective to the findings on the origin and evolution of the process of translation. This book provides insight into the evolution of the translation process and machinery from a modern perspective. Written by leading experts in molecular biology, this text looks into the origins and evolution of the protein synthetic machinery.
Author: Olivier Binda
Publisher: Academic Press
ISBN: 012802609X
Category : Science
Languages : en
Pages : 468
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Book Description
Chromatin Signaling and Diseases covers the molecular mechanisms that regulate gene expression, which govern everything from embryonic development, growth, and human pathologies associated with aging, such as cancer. This book helps researchers learn about or keep up with the quickly expanding field of chromatin signaling. After reading this book, clinicians will be more capable of explaining the mechanisms of gene expression regulation to their patients to reassure them about new drug developments that target chromatin signaling mechanisms. For example, several epigenetic drugs that act on chromatin signaling factors are in clinical trials or even approved for usage in cancer treatments, Alzheimer's, and Huntington's diseases. Other epigenetic drugs are in development to regulate various class of chromatin signaling factors. To keep up with this changing landscape, clinicians and doctors will need to stay familiar with genetic advances that translate to clinical practice, such as chromatin signaling. Although sequencing of the human genome was completed over a decade ago and its structure investigated for nearly half a century, molecular mechanisms that regulate gene expression remain largely misunderstood. An emerging concept called chromatin signaling proposes that small protein domains recognize chemical modifications on the genome scaffolding histone proteins, facilitating the nucleation of enzymatic complexes at specific loci that then open up or shut down the access to genetic information, thereby regulating gene expression. The addition and removal of chemical modifications on histones, as well as the proteins that specifically recognize these, is reviewed in Chromatin Signaling and Diseases. Finally, the impact of gene expression defects associated with malfunctioning chromatin signaling is also explored. - Explains molecular mechanisms that regulate gene expression, which governs everything from embryonic development, growth, and human pathologies associated with aging - Educates clinicians and researchers about chromatin signaling, a molecular mechanism that is changing our understanding of human pathology - Explores the addition and removal of chemical modifications on histones, the proteins that specifically recognize these, and the impact of gene expression defects associated with malfunctioning chromatin signaling - Helps researchers learn about the quickly expanding field of chromatin signaling
Author: Ramona Weber
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
All living systems rely on appropriate protein synthesis and therefore evolved intricate mechanisms to control their proteome. Especially, the complexity of metazoan multicellular processes requires a strict and multilayered regulation of gene expression at the level of transcription, mRNA processing, translation, mRNA stability, and protein modifications and stability. Here, I present work on two research projects that uncovered the hitherto unidentified roles of translation initiation (1) and mRNA decay factors (2) specialized in controlling unconventional mRNA translation and co-translational mRNA stability, respectively. The initiation step of translation commences with the assembly of the eukaryotic initiation factor 4F (eIF4F) complex on the mRNA 5 ́ cap structure which facilitates the recruitment of the ribosome to mediate protein synthesis. The eIF4F consists of the cap-binding protein eIF4E, the RNA helicase eIF4A and the scaffolding factor eIF4G. Apart from eIF4G, metazoan cells express other eIF4G-like proteins: eIF4G2 - a.k.a. DAP5/p97/NAT1 - and eIF4G3. Although the different homologs perform non-redundant functions in translation, we lack detailed understanding of their individual contribution to the initiation of protein synthesis. To gain insights into the function of DAP5 in translation initiation, I applied transcriptome (RNA- sequencing) and translatome (ribosome profiling) approaches to CRISPR-Cas9 engineered human HEK293T DAP5-null cells. These approaches allowed the identification of a group of mRNAs with complex 5 ́ untranslated regions (UTRs) that required the DAP5-eIF4A complex for efficient translation. In detail, the 5 ́ UTRs of DAP5 targets harbor strong secondary structures and at least one upstream open reading frame (uORF) that normally sequesters ribosomes from initiation at the main ORF (mORF). In this context, DAP5 is critical for mORF translation as it mediates re-initiation after uORF translation. Taken together, my studies on DAP5 demonstrate how cells control translation initiation using 5 ́ UTR-associated mechanisms. Regulation of translation initiation can also involve additional cap-binding proteins. The eIF4E-homologous protein (4EHP) competes with eIF4E to bind the mRNA 5 ́ cap structure. Unlike eIF4E, 4EHP does not promote translation since it is unable to recruit eIF4G and the ribosome. Instead, 4EHP represses translation and induces mRNA decay with the help of 4EHP-binding factors. The GIGYF1 and GIGYF2 proteins specifically associate with 4EHP and act as scaffolding proteins for GYF domain-associated proteins like tristetraprolin (TTP) or ZNF598, the RNA helicase and decapping activator DDX6, and NOT1 - a subunit of the CCR4-NOT deadenylase complex. When recruited to an mRNA, the 4EHP-GIGYF1/2 6 complexes thus elicit translation repression and mRNA decay. Although the molecular mechanisms have been studied in great detail, we only have sparse information on the pool of mRNAs subjected to 4EHP-GIGYF1/2 mediated repression and decay. Analysis of RNA- sequencing and ribosome profiling datasets of 4EHP- and GIGYF1/2-null cells revealed that the 4EHP-GIGYF1/2 complexes co-translationally target mRNAs with perturbed ribosome elongation or specific nascent peptide chains for decay. These include, among others, mRNAs encoding endoplasmic reticulum (ER)-targeted proteins, a- and b-tubulin subunits and mRNAs with CAG codon repeats encoding poly-glutamine (Q) stretches. In detail, the 4EHP- GIGYF1/2 complexes are recruited to target mRNAs via the GYF domain-associated proteins and upon binding to the mRNA 5 ́ cap, and DDX6, degrade the bound mRNA. My studies show for the first time how a repressive complex, associated with neurological disorders in animal models and affected humans, specifically minimizes the protein output of a subset of mRNAs. Altogether, I identified a previously unappreciated role of the 4EHP-GIGYF1/2 complexes in maintaining protein homeostasis and preventing excessive production of potentially toxic proteins. In summary, my studies increase our understanding of how metazoan cells utilize the translation control toolbox to fine-tune their proteome and react to developmental cues, adapt to environmental changes and maintain homeostasis. The identified translational programs are fundamental for establishing a multicellular organization but at the same time allow the organism to evade cancer and neurological diseases.
Author: Nahum Sonenberg
Publisher: CSHL Press
ISBN: 9780879696184
Category : Gene expression
Languages : en
Pages : 1034
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Book Description
Since the 1996 publication of Translational Control, there has been fresh interest in protein synthesis and recognition of the key role of translation control mechanisms in regulating gene expression. This new monograph updates and expands the scope of the earlier book but it also takes a fresh look at the field. In a new format, the first eight chapters provide broad overviews, while each of the additional twenty-eight has a focus on a research topic of more specific interest. The result is a thoroughly up-to-date account of initiation, elongation, and termination of translation, control mechanisms in development in response to extracellular stimuli, and the effects on the translation machinery of virus infection and disease. This book is essential reading for students entering the field and an invaluable resource for investigators of gene expression and its control.
Author: Sam Thiagalingam
Publisher: Cambridge University Press
ISBN: 0521493390
Category : Mathematics
Languages : en
Pages : 597
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Book Description
An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.
Author: Armen Parsyan
Publisher: Springer
ISBN: 9401790787
Category : Medical
Languages : en
Pages : 709
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Book Description
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.
Author: Zeljka Smit McBride
Publisher:
ISBN:
Category :
Languages : en
Pages : 254
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Book Description
Author: R. Perez-Bercoff
Publisher: Springer
ISBN: 9781468441260
Category : Medical
Languages : en
Pages : 501
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Book Description
vi The word ppotein, coined one and a half century ago from the 1TpOTE:toa ("proteios" = of primary importance), underlines the "primary importance" ascribed to proteins from the time they were described as biochemical entities. But the unmatched compl~xity of the process involved in their biosynthesis was (understandably) overlooked. Indeed, protein biosynthesis was supposed to be nothing more than the reverse of protein degradation, and the same enzymes known to split a protein into its constituent amino acids were thought to be able, under adequate conditions, to reconstitute the peptide bond. This oversimplified view persisted for more than 50 years: It was just in 1940 that Borsook and Dubnoff examined the thermodynamical aspects of the process, and concluded that protein synthesis could not be the reverse of protein degradation, such an "uphill task being thermody namically impossible ••• • " The next quarter of a century witnessed the unravelling of the basic mechanisms of protein biosynthesis, a predictable aftermath of the Copernican revolution in biology which followed such dramatic de velopments as the discovery of the nature of the genetic material, the double helical structure· of DNA, and the determination of the ge netic code. Our present understanding of the sophisticated mechan isms of regulation and control is a relatively novel acquisition, and recent studies have shed some light into the structure and organi zation of the eukaryotic gene.
Author: Antonius M. VanDongen
Publisher: CRC Press
ISBN: 142004415X
Category : Medical
Languages : en
Pages : 368
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Book Description
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
