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Chapter 18 - Oncogenes
- from SECTION 2 - MOLECULAR PATHOLOGY
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- By Natalie A Whalley, PhD, lectures in the Division of Molecular Medicine and Haematology, School of Pathology, University of the Witwatersrand., Kate Hammond, BSc (Hons), MT, PhD, is Professor of Molecular Medicine and Haematology, University of the Witwatersrand.
- Edited by Barry Mendelow, University of the Witwatersrand, Johannesburg, Michèle Ramsay, University of the Witwatersrand, Johannesburg, Nanthakumarn Chetty, University of the Witwatersrand, Johannesburg, Wendy Stevens, University of the Witwatersrand, Johannesburg
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- Book:
- Molecular Medicine for Clinicians
- Published by:
- Wits University Press
- Published online:
- 04 June 2019
- Print publication:
- 01 October 2008, pp 218-226
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Summary
INTRODUCTION
The cell is a complex array of networks – a protein communication system, with phosphorylation cascades transmitting messages from receptors at the surface to the nucleus. Individual proteins integrate signals from a diversity of activator molecules, transducing them through intracellular signalling pathways to various target or effector proteins. Circuits of this nature enable a cell to respond to external factors and to modify its own function. In particular, in this chapter we will look at the way in which growth factors and hormones regulate the processes of cell division and differentiation, and cell survival.
Proto-oncogenes have been identified as genes encoding protein members of cascades dedicated to the transmission of signals regulating growth and survival. The actions of proto-oncogene-encoded proteins are tightly controlled under normal circum stances. If such proteins are abnormal, or if there is too much of them, signals are deregulated, downstream transducing molecules are activated and there is excessive stimulation of cell growth and survival. When intracellular signal pathways are out of control, a cell may begin to multiply unceasingly in a way that can lead to cancer.
We define a proto-oncogene as the form the gene takes as it carries out its usual functions within a cell – it has the potential to become an oncogene. Proto-oncogenes may also be referred to as cellular oncogenes (conc). An oncogene is a mutated form of a proto-oncogene producing a protein, which stimulates uncontrolled growth and promotes cell survival. The homologous counterparts of certain oncogenes occur in retroviruses; these are viral oncogenes (v-onc). Oncogenes are dominant in the sense that only one allele needs to be mutated to cause cancer.
Many of the human oncogenes were discovered through the study of animal retro - viruses, acutely transforming RNA tumour viruses, whose genomes are reverse transcribed into DNA in infected cells. During the course of infection, retroviral DNA is inserted into the chromosomes of host cells. The retro viral oncogenes are derived from the normal cellular genes of the host which have been incorporated into the retroviral genome. In 1970, the first oncogene, now known as the SRC oncogene, was identified in a chicken tumour virus.
Chapter 3 - The Anatomy and Physiology of the Genome
- from Section 1 - Principles Of Cellular And Molecular Biology
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- By Marc S Weinberg, PhD, is a senior lecturer in the Division of Molecular Medicine and Haematology, University of the Witwatersrand, and a member of the Antiviral Gene Therapy Research Unit., Natalie A Whalley, PhD, lectures in the Division of Molecular Medicine and Haematology, School of Pathology, University of the Witwatersrand., Michèle Ramsay, PhD (Human Genetics), is currently Professor and Head of the Molecular Genetics Laboratory, Division of Human Genetics, National Health Laboratory Service and University of the Witwatersrand.
- Edited by Barry Mendelow, University of the Witwatersrand, Johannesburg, Michèle Ramsay, University of the Witwatersrand, Johannesburg, Nanthakumarn Chetty, University of the Witwatersrand, Johannesburg, Wendy Stevens, University of the Witwatersrand, Johannesburg
-
- Book:
- Molecular Medicine for Clinicians
- Published by:
- Wits University Press
- Published online:
- 04 June 2019
- Print publication:
- 01 October 2008, pp 19-36
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Summary
INTRODUCTION
The genome represents the entire genetic complement of an organism and is a repository of biological information, which is used to create and sustain every living system. Typically, a genome is composed of nucleic acids, with deoxyribonucleic acid or DNA being the most common form, although some viral genomes are composed of ribonucleic acid or RNA. DNA is a polymeric chain defined by a sequence of monomeric units called nucleotides. The asymmetrical arrangement of the nucleotide sequence of DNA or RNA represents a ‘code’ that defines the functional and structural role of a genome within an organism. It is therefore not surprising that the genome is frequently referred to as the ‘blueprint of life’.
Although all living organisms contain genomes, the focus of this chapter will be on the human genome, which is composed of two distinct sections: nuclear and mitochondrial. The nuclear genome is by far the largest section and comprises about 3.2 billion nucleotides, which are divided into 24 linear molecules of DNA arranged into structures called chromosomes. The mitochondrial genome is a much smaller circular molecule of DNA comprising 16 569 nucleotides. Many mitochondrial organelles are found within a cell, allowing for multiple (approximately 8000) copies of this genome to be present.
Mere numbers can often deceive one, since everything operates at the molecular level. This molecular scale needs to be appreciated better. For example, there are over 100 000 000 000 000 cells in a typical adult human, and most cells have two complete copies (diploid) of the nuclear genome. If one were to convert the sequence of nucleotides into alphabetical letters this would equate to approximately 3000 volumes of Gray's Anatomy per cell! The past two decades have seen the completion of the sequencing of the human genome, a monu - mental scientific feat. However, we are now faced with the challenge of deciphering this code, a task that brings biology and medicine into the realm of the information sciences. This phenomenon is not dissimilar to the evolution of the computer that led to the development of information technology and the modern digital revolution.
Chapter 4 - Molecular Cell Biology
- from Section 1 - Principles Of Cellular And Molecular Biology
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- By Natalie A Whalley, PhD, lectures in the Division of Molecular Medicine and Haematology, School of Pathology, University of the Witwatersrand., Sarah Walters, BSc (Hons), MSc (Med) (Genetic Counselling), worked as a genetic counsellor in the Division of Human Genetics, University of the Witwatersrand, from 2001 to 2007. In 2007 she became Honorary Treasurer of the Southern African Inherited Disorders Association and began setting up the Birth Defects and Disabilities Foundation (BDDF). She is currently coordinator of the BDDF and programme director of the Medical Genetics Education Programme for registered nurses., Kate Hammond, BSc (Hons), MT, PhD, is Professor of Molecular Medicine and Haematology, University of the Witwatersrand.
- Edited by Barry Mendelow, University of the Witwatersrand, Johannesburg, Michèle Ramsay, University of the Witwatersrand, Johannesburg, Nanthakumarn Chetty, University of the Witwatersrand, Johannesburg, Wendy Stevens, University of the Witwatersrand, Johannesburg
-
- Book:
- Molecular Medicine for Clinicians
- Published by:
- Wits University Press
- Published online:
- 04 June 2019
- Print publication:
- 01 October 2008, pp 37-49
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Summary
INTRODUCTION
The cell is a dynamic system – a vast array of inter acting molecules forming complex metabolic networks in continuous motion. Proteins are the active molecules transforming the information encoded in genomic DNA into function, enabling and regulating cell life – division, differentiation, communication – and death.
The complement of proteins within a cell at any given time may exceed 400 000. These molecules have many diverse roles. They may be extracellular messengers, such as hormones or growth factors, they may be ion channels or membrane receptors for hormones, growth factors or neurotransmitters, they may function as enzymes or response elements within the cell, or they may be regulators of nuclear transcription. In medicine, most of the differences between tissues in health and disease are seen at the protein level.
In this chapter, we will focus on the cell cycle, cell division and differentiation, and programmed cell death or apoptosis. We will explore the cellular communication networks that regulate these processes and consider the actions of certain of the proteins involved in the systems. But first, because it is such an important mechanism in the control of cellular activity, we begin with a brief discussion of protein phosphorylation.
PROTEIN PHOSPHORYLATION
The presence of phosphate in protein molecules was known more than a century ago but only in the 1950s, as a result of independent studies of Sutherland and co-workers and Fischer and Krebs, was its vital functional importance recognised. Since that time, more and more phosphate-containing proteins, protein kinases and phosphoprotein phosphatases continued to be identified at an everincreasing rate.
The reversible phosphorylation of proteins influences virtually all cellular functions and is an essential mechanism in the control of life processes. Many proteins are activated or inactivated by the simple transfer of a phosphate group from one molecule to another. Some proteins are activated by phosphorylation while others are inactivated.