Chapter 20 Flashcards
Cancer
Why are missense mutations leading to the same amino acid change frequently found in oncogenes?
Only a limited number of mutations in a few selective sites lead to oncogenes with gain of function.
Why nonsense mutations leading to truncation of the protein sequence by creating premature stop codons or nonsense codons often predominate in tumor suppressor genes together with missense mutations in domains that bind a transcription regulator?
Multiple and more randomly occurring mutations lead to tumour suppressor genes with loss of function.
These include both missense mutations that might change how the protein interacts with other proteins or nonsense mutations that might truncate critical parts of the protein.
Explain the concept of driver mutations and passenger mutations in cancer research
Driver mutations are causal factors in the development of cancer whereas passenger mutations are irrelevant for the development of cancer, but happen to have occurred in the same cell because of genetic instability.
In cancer research it is critical to find methods, such as frequency of occurrence.
Explain the role of Retinoblastoma (Rb) in control of the cell cycle and why the gene encoding this protein is regarded as a tumor suppressor gene
The Retinoblastoma protein bind E2F and thereby prevent transcription of E2F mediated factors important for entry of the cell into late G1 and S phases. Upon phosphorylation, Rb release E2F and thereby regulate cell cycle progression. Rb is regarded as a tumour suppressor gene because it is a suppressor of the cell cycle and cell proliferation. HPV express a viral oncogene that encodes the E7 protein that tightly bind Rb and thereby drive proliferation by the resulting increase in the free pool of E2F.
What is Ras and what is its function?
Oncogene
Ras is a protein that plays a major part in in the RTK (Receptor tyrosine kinase signalling system). The role of Ras when activated by SH3 domain binding is to induce growth of cells and enabling the transcription of genes. It is also involved in the MAP-Kinase pathway that signals growth promotor gene transcriptions. This property of Ras is the reason it is considered as an oncogene. Certain RTK pathways also stimulate the activation of anti-apoptotic proteins and enabling cell survival
How can you observe that cells undergo apoptosis rather than necrosis?
Caspases are activated during apoptosis and cleave intracellular substrates that give rise to the morphological changes observed
The cytoplasm and nucleoplasm have fragmented forming apoptotic bodies – a process called blebbing. The apoptotic bodies are normally phagocytosed by other cells (e.g. macrophages) and are thereby eliminated without triggering an immune response.
In contrast, cells dying by necrosis releases intracellular component that trigger an inflammatory response.
Explain the distinction between intrinsic and extrinsic signaling pathways that regulate apoptosis
Intrinsic pathways are those that eventually release cytochrome c from mitochondria and trigger apoptosis by cytochrome c dependent activation of caspases.
Extrinsic signaling pathways that regulate apoptosis are those that activate caspases independently of mitochondria via direct activation of caspases by factors associated with death receptors.
Describe how a DNA damage response induces apoptosis
Upon DNA damage, p53 activated the transcription of BH3-only proteins such as PUMA and Noxa. They bind to and inhibit the anti-apoptotic factor Bcl-2 and thereby activate apoptosis.
Describe how the concept of synthetic lethality can be used in cancer treatment
Synthetic lethality refer to two genetic loss-of-function events, either of which alone is compatible with viability, but together in the same cell result in lethality. Cancer cells with loss-of-function mutations in DNA damage repair pathway have a greater dependency on the remaining pathways. Thus, anti-cancer drugs that inhibit the remaining pathways can be used to preferentially kill cancer cells and spare normal cells.
What is oligomerization?
The formation of an oligomer
An oligomer consists of a few monomer units, like dimers and trimers are oligomers.
What is a DNA tumor virus (oncovirus)?
Virus that can cause cancer
DNA oncoviruses transform infected cells by integrating their DNA into the host cell’s genome.[37] The DNA is believed to be inserted during transcription or replication, when the two annealed strands are separated
Tends to target p53 and Rb
(as they regulate the transition between G1 and S-phase, arresting the cell before DNA replication)
What is multidrug resistence?
b) Phenomenon in which a cell becomes insensitive not only to a drug it has been treated
What is Human Papillomavirus (HPV)?
a) The cause of human warts and a causative factor in carcinomas of the uterine cervix
What are carcinogens?
A substance capable of causing cancer in living tissue
What are oncogenes and why are they a target for cancer therapy?
A gene that has the potential to cause cancer. In tumor cells, they are often mutated and/or expressed at high levels
Oncogenes a hyperactive signal which a potential inhibitor aims to turn off
