Characterization of the Transcription Corepressor C Terminal Binding Protein (CtBP) PDF Download
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Author: Vivek Kumar
Publisher:
ISBN:
Category :
Languages : en
Pages : 288
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Author: Vivek Kumar
Publisher:
ISBN:
Category :
Languages : en
Pages : 288
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Author: Priya Mani
Publisher:
ISBN:
Category : Drosophila
Languages : en
Pages : 326
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Author: Mario Ramiro Calderon
Publisher:
ISBN:
Category :
Languages : en
Pages :
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"Gene transcription is highly regulated by proteins called transcription factors, which bind to specific DNA sequences, and recruit a plethora of cofactors that directly modify the chemical composition of N-terminal histone tails or recruit enzymes that do so. These modifications alter the structure of chromatin, and can prime it for or render it refractory to transcription. Many of these recruited cofactors, termed transcriptional coactivators or corepressors, can interact with several classes of transcription factors. Initially characterized as an inhibitor of nuclear receptor-mediated transactivation, Ligand-dependent CoRepressor (LCoR) represses transcription through recruitment of specific C-terminal binding proteins (CtBPs) and histone deacetylases (HDACs) via defined domains. We were interested in determining whether LCoR also serves as a coregulator of other classes of transcription factors. Using yeast two-hybrid screens with the open reading frame of LCoR as bait, we found novel interactions with the transcription factor Krüppel-like factor 6 (KLF6) and another transcriptional coregulator Krüppel-Associated Box (KRAB)-associated protein 1 (KAP-1). KLF6 may act as a tumour suppressor in certain malignancies, while KAP-1 is a corepressor that functions through many zinc finger transcription factors. Functional characterization of these interactions revealed that LCoR regulates the expression of the genes cyclin-dependent kinase inhibitor 1A (CDKN1A) and cadherin 1 (CDH1) in specific prostate cancer cells via KLF6, and growth arrest and DNA-damage-inducible alpha (GADD45A) and fibroblast growth factor 2 (FGF2) in specific breast cancer cells through KAP-1. CDKN1A expression is regulated by the hormone insulin-like growth factor 1 (IGF-1) in certain cell types, and levels of IGF-1 and CDKN1A are elevated in prostate cancer. We found that LCoR and CDKN1A levels were enhanced in prostate cancer tissue and in IGF-1 treated prostate cancer cells. Additionally, the transcriptional response of a complex composed of KLF6 and LCoR may be altered by IGF-1 as we found that treatment of prostate cancer cells transiently overexpressing KLF6 and LCoR with IGF-1 abrogated their repression of a reporter gene. Hence, IGF-1-mediated transcriptional expression of CDKN1A may occur through KLF6 and LCoR and have implications for prostate cancer development. Similarly, the expression of FGF2 is frequently lost and associated with a more malignant phenotype in breast cancer. Our results show that a transcriptional complex composed of LCoR, KAP-1, and the transcription factor ZBRK1 suppresses the expression of the FGF2 gene in breast cancer cells, which enhanced cell viability. The identification of this transcriptional silencing complex provides a mechanism for the lack of expression of FGF2 in breast cancer. The work presented in this thesis contains four major contributions to further the understanding of the biological function of LCoR. In addition to identifying novel molecular interactions with (1) KLF6 and (2) KAP-1, which illustrate that LCoR can function in transcription independent of nuclear receptors, the functional characterization of these interactions revealed potential roles for LCoR in (3) breast and (4) prostate tumour development." --
Author: G. Chinnadurai
Publisher: Springer
ISBN: 9781441922960
Category : Medical
Languages : en
Pages : 0
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Book Description
This book is a comprehensive monograph on the CtBP family proteins. These proteins are gaining wide scientific interest due to their critical roles in animal development and in oncogenesis. The CtBP family proteins are multifunctional. They predominantly function as transcriptional corepressors in the nucleus by recruiting various histone modifying enzymes such as histone deacetylases, histone methylases and a histone demethylase. They also perform several diverse cytosolic functions such as Golgi maintenance and in central nervous system synapses.
Author: Anders Sundqvist
Publisher: Uppsala Universitet
ISBN: 9789155451448
Category : Medical
Languages : en
Pages : 50
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Book Description
Author: G. Chinnadurai
Publisher: Springer Science & Business Media
ISBN: 0387399739
Category : Medical
Languages : en
Pages : 131
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Book Description
The Ctbp family proteins are multifunctional. They predominantly function as transcriptional corepressors in the nucleus by recruiting various histone modifying enzymes such as histone deacetylases, histone methylases and a histone demethylase. This book is a comprehensive monograph on the Ctbp family proteins.
Author: Justin Robert Prigge
Publisher:
ISBN:
Category : Protein binding
Languages : en
Pages : 214
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Book Description
Recruitment of the TATA-Binding Protein, TBP, to the promoter is a critical, rate-limiting step that drives the initial phase of nearly all gene transcription events. Because of this, many transcriptional regulators target TBP, either to localize TBP at the promoter, or to relay signals between other promoter-bound protein complexes and the basal transcription machinery. Studies described herein were designed to identify novel protein-protein interactions with TBP. To do this, we screened mid-gestational pregnancy-associated cDNA prey libraries using two different yeast two-hybrid systems. Screens in both systems revealed both known and novel TBP interactors. B'-Related Factor 1 and Transcription Factor II A were identified in screens that used full-length TBP as bait. These proteins are known to interact with TBP and thus validated our system. In addition to known interactors, novel interactions with both the N-terminal (TBP-N) and C-terminal (TBP-C) domains of TBP were identified. Coactivator- Associated Arginine Methyltransferase 1 (CARM1), Pax Transactivation Domain- Interacting Protein (PTIP), and Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Factor (LITAF) all interacted with TBP-N. Proteins that interacted with TBP-C were Huntingtin-Associated Protein 1 (HAP1), four members of the Protein Inhibitor of Activated STAT (PIAS) family of transcriptional regulatory proteins, and Zinc Finger Protein 523 (ZFP523). The TBP interaction domains on PIAS1 and HAP1 were mapped to further define each interaction. Mapping studies revealed that TBP interacts with a single region on PIAS1, and with two separate regions on HAP1. We also show that TBP co-precipitates with PIAS1, PIAS3, HAP1, and PTIP. In conclusion, our studies, in agreement with previous published data suggest that TBP interacts with many classes of regulatory proteins, including transcriptional activators, repressors, and individual components of the transcriptional co-regulatory complexes. They also support the hypothesis that the TBP N-terminus is a protein interaction module and may provide clues to the function of the vertebrate-specific N terminus of TBP.
Author: Kensal Edward Van Holde
Publisher: Prentice Hall
ISBN:
Category : Science
Languages : en
Pages : 342
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Author: Tilman Borggrefe
Publisher: Springer
ISBN: 3319895125
Category : Science
Languages : en
Pages : 417
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Book Description
This book describes the Notch signaling pathway with a focus on molecular mechanisms. The Notch signaling pathway is a seemingly simple pathway that does not involve any second messenger. Upon ligand binding two consecutive proteolytic cleavages of the NOTCH receptor release the Notch intracellular domain from the membrane. The Notch intracellular domain migrates into the nucleus and activates gene expression. Recently, new technologies allowed us to better understand this pivotal signaling cascade and revealed new regulatory mechanisms. The different chapters cover many aspects of the Notch signaling focusing on the mechanisms governing the receptor/ligand interaction as well as on the downstream intracellular signaling events. Aspects of both canonical and non-canonical signaling are discussed and the function of Notch signaling in physiological and pathological contexts are elucidated. This book is not only intended for experts but it should also be a useful resource for young, sprouting scientists or interested scientists from other research areas, who may use this book as a stimulating starting point for further discoveries and developments.
Author: Martin L. Privalsky
Publisher: Springer Science & Business Media
ISBN: 3662105950
Category : Medical
Languages : en
Pages : 202
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Book Description
Corepressors are newly discovered assemblies of proteins that play essential roles in eukaryotic gene regulation. Recent discoveries about corepressors have provided new insights into the molecular basis of gene regulation, and have established surprising connections between the mechanisms of action of a wide variety of transcriptional regulators. The reviews in this volume critically discuss the nature, mechanisms of action, and physiological roles of corepressors in a diverse assortment of biological systems. Both basic and clinical investigators will be able to find relevant information. The comprehensive nature of the compilation, and the breadth of the reviews, are intended to provide the reader with an excellent introduction to the newly emergent and rapidly-growing field of corepressor research. A valuable and detailed reference guide.
