Methylation of the Retinoblastoma Tumor Suppressor by SMYD2 and Functional Interactions Between Retinoblastoma and C-MYC in a Mouse Model of Hepatocellular Carcinoma
Title | Methylation of the Retinoblastoma Tumor Suppressor by SMYD2 and Functional Interactions Between Retinoblastoma and C-MYC in a Mouse Model of Hepatocellular Carcinoma PDF eBook |
Author | Louis Alexander Saddic (III.) |
Publisher | Stanford University |
Pages | 104 |
Release | 2011 |
Genre | |
ISBN |
The retinoblastoma tumor suppressor RB is a central cell cycle regulator. Here we demonstrate that RB can be methylated by SMYD2 at lysine 860, a highly conserved and novel site of modification. This methylation event occurs in vitro and in cells and is regulated during cell cycle progression, cellular differentiation, and in response to DNA damage. Furthermore, we show that RB mono-methylation at lysine 860 provides a direct binding site for the methyl-binding domain of the transcriptional repressor L3MBTL1. This modification may be crucial for regulating the function of RB as a tumor suppressor. Inactivation of RB and activation of the MYC family of oncogenes are frequent events in a large spectrum of human cancers. Here, we sought to also test whether loss of RB function would affect cancer development in a mouse model of c-MYC-induced hepatocellular carcinoma (HCC). We found that RB inactivation has minimal effects on the cell cycle, cell death, and differentiation features of liver tumors driven by increased levels of c-MYC. However, combined loss of RB and activation of c-MYC led to an increase in polyploidy in mature hepatocytes before the development of tumors and a trend for decreased survival after cancer initiation.
Methylation of the Retinoblastoma Tumor Suppressor by SMYD2 and Functional Interactions Between Retinoblastoma and C-MYC in a Mouse Model of Hepatocellular Carcinoma
Title | Methylation of the Retinoblastoma Tumor Suppressor by SMYD2 and Functional Interactions Between Retinoblastoma and C-MYC in a Mouse Model of Hepatocellular Carcinoma PDF eBook |
Author | Louis Alexander Saddic (#suffix.) |
Publisher | |
Pages | |
Release | 2011 |
Genre | |
ISBN |
The retinoblastoma tumor suppressor RB is a central cell cycle regulator. Here we demonstrate that RB can be methylated by SMYD2 at lysine 860, a highly conserved and novel site of modification. This methylation event occurs in vitro and in cells and is regulated during cell cycle progression, cellular differentiation, and in response to DNA damage. Furthermore, we show that RB mono-methylation at lysine 860 provides a direct binding site for the methyl-binding domain of the transcriptional repressor L3MBTL1. This modification may be crucial for regulating the function of RB as a tumor suppressor. Inactivation of RB and activation of the MYC family of oncogenes are frequent events in a large spectrum of human cancers. Here, we sought to also test whether loss of RB function would affect cancer development in a mouse model of c-MYC-induced hepatocellular carcinoma (HCC). We found that RB inactivation has minimal effects on the cell cycle, cell death, and differentiation features of liver tumors driven by increased levels of c-MYC. However, combined loss of RB and activation of c-MYC led to an increase in polyploidy in mature hepatocytes before the development of tumors and a trend for decreased survival after cancer initiation.
The Retinoblastoma Protein
Title | The Retinoblastoma Protein PDF eBook |
Author | Pedro G. Santiago-Cardona |
Publisher | Humana Press |
Pages | 200 |
Release | 2018-02-22 |
Genre | Medical |
ISBN | 9781493975648 |
This volume covers the mechanisms of pRb inactivation detailing repressive mechanisms commonly associated to cancer, and representative of the experimentally relevant tests used in the establishment of cancer diagnosis and prognosis. Chapters contain protocols and in-depth discussions for commonly used experimental approaches to assess the status and function of components of the pRb pathway, including pRb itself, in cell lines and biological samples.Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, The Retinoblastoma Protein aims to serve as a guide to assist molecular cancer biologists in their search for understanding of the molecular functions of this preeminent tumor suppressor.
DNA and Histone Methylation as Cancer Targets
Title | DNA and Histone Methylation as Cancer Targets PDF eBook |
Author | Atsushi Kaneda |
Publisher | Springer |
Pages | 616 |
Release | 2017-09-04 |
Genre | Medical |
ISBN | 3319597868 |
This book will focus on DNA and histone methylation in epigenetics and describe how it is involved in the molecular mechanisms responsible for the development of cancer. Chapters will summarize the current knowledge of the molecular basis of DNA and histone methylation and explain how it is involved in cancer, describe the features of DNA and histone methylation associated with particular types of cancer, diagnostic/therapeutic applications, and future directions of DNA and histone methylation as cancer targets.
Toxicoepigenetics
Title | Toxicoepigenetics PDF eBook |
Author | Shaun D. McCullough |
Publisher | Academic Press |
Pages | 430 |
Release | 2018-11-02 |
Genre | Medical |
ISBN | 0128124342 |
Toxicoepigenetics: Core Principles and Applications examines the core aspects of epigenetics, including chromatin biology, DNA methylation, and non-coding RNA, as well as fundamental techniques and considerations for studying each of these mechanisms of epigenetic regulation. Although its integration into the field of toxicology is in its infancy, epigenetics have taken center stage in the study of diseases such as cancer, diabetes, and neurodegeneration. Increasing the presence of epigenetics in toxicological research allows for a more in-depth understanding of important aspects of toxicology such as the role of the environment and lifestyle influencing the individual susceptibility to these effects and the trans-generational transmission of these health effects and susceptibilities. Methods chapters are included to help improve efficacy and efficiency of protocols in both the laboratory and the classroom. Toxicoepigenetics: Core Principles and Applications is an essential book for researchers and academics using epigenetics in toxicology research and study. Introduces the fundamental principles and practices for understanding the role of the epigenome in toxicology Presents the foundation of epigenetics for toxicologists with a broad range of backgrounds Discusses the incorporation of epigenetics and epigenomics into current toxicological studies and interpretation of epigenetic data in toxicological applications
Gene and Cell Therapy: Biology and Applications
Title | Gene and Cell Therapy: Biology and Applications PDF eBook |
Author | Giridhara R. Jayandharan |
Publisher | Springer |
Pages | 316 |
Release | 2018-09-12 |
Genre | Medical |
ISBN | 9811304815 |
Recent advances in stem cell biology, nanotechnology and gene therapy have opened new avenues for therapeutics. The availability of molecular therapeutics that rely on the delivery of DNA, RNA or proteins, harnessing enhanced delivery with nanoparticles, and the regenerative potential of stem cells (adult, embryonic or induced pluripotent stem cells) has had a tremendous impact on translational medicine. The chapters in this book cover a range of strategies for molecular and cellular therapies for human disease, their advantages, and central challenges to their widespread application. Potential solutions to these issues are also discussed in detail. Further, the book addresses numerous advances in the field of molecular therapeutics that will be of interest to the general scientific community. Lastly, the book provides specific examples of disease conditions for which these strategies have been transferred to the clinic. As such, it will be extremely useful for all students, researchers and clinicians working in the field of translational medicine and molecular therapeutics.
Prostate Cancer
Title | Prostate Cancer PDF eBook |
Author | Scott M. Dehm |
Publisher | Springer Nature |
Pages | 483 |
Release | 2020-01-03 |
Genre | Medical |
ISBN | 303032656X |
The purpose of this book is to provide a contemporary overview of the causes and consequences of prostate cancer from a cellular and genetic perspective. Written by experts in the fields of epidemiology, toxicology, cell biology, genetics, genomics, cell-cell interactions, cell signaling, hormone signaling, and transcriptional regulation, the text covers aspects of prostate cancer from disease initiation to metastasis. Chapters explore in depth the cells of origin for prostate cancer, its genomic subtypes, neural transcription factors in disease progression, epigenetic regulation of chromatin, and many other topics. This book distinguishes itself from other texts on prostate cancer by its focus on cellular and genetic mechanisms, as opposed to clinical diagnosis and management. As a result, this book will be of broad interest to basic and translational scientists with familiarity of these topics, as well as to trainees at earlier stages of their research careers.