Biochemistry Lecture 12 - Cancer Flashcards
What are the hallmarks of cancers?
Disordered proliferation, growth, and differentiation of cells.
Describe the Rb mechanism.
Cyclins D and E form their complexes with Cdks, and can then add phosphate groups to Rb. This inactivates Rb, which causes the release of transcription factor E2F. E2F can then take part in transcribing genes for proteins involved in DNA replication.
How does a Rb gene mutation result in increased cell proliferation?
A mutated Rb does not sequester E2F, allowing for transcription of genes that encode products involved in DNA synthesis.
Describe the p53 mechanism.
p53 is the substrate for many phosphorylation events under stress, such as during DNA mistakes. After phosphorylation, it binds to enhancer DNA regions and induces transcription of the p21 gene, whose products bind to cyclin/cdk complexes to halt the cell cycle. P21 products can also bind to PCNA to stop replication forks.
Can p53 trigger apoptosis?
Yes.
How many alleles of a proto-oncogene need to mutate for tumorigenesis?
Only one.
What is ErbB/HER2 and how it is involved in cancer?
It is an epidermal growth factor receptor and a mutated one can constantly signal transduce even without ligand present, promoting cell growth.
Describe the RAS mechanism. Is it a tumor suppressor gene or a proto-oncogene?
RAS is a cytoplasmic signaling molecule. When bound to GDP, it is off. When bound to GTP, it sends signals. Mutations involved in downregulating GTPase or GTPase activity effectively keep RAS in the on position, promoting cell growth. It is a proto-oncogene.
How does the NF1 gene lead to cancer? It is a tumor suppressor gene or a proto-oncogene?
It codes for a protein, Neurofibromin, which contains a GAP domain (GTPase activating protein). When mutated, this allows RAS to stay bound to GTP, in the on position. It is a tumor suppressor gene.
What are Fos and Jun and how are they involved in cancer? What are their binding sites called?
Fos and Jun are transcription factors. In normal states, they result in transient growth. If overexpressed, they can result in continuous growth. They bind to AP1 sites on DNA.
What is the Myc gene and what happens with it in Burkitt’s Lymphoma? Is it considered an oncogene or tumor suppressor?
The Myc gene encodes a transcription factor that regulates ~15% of all genes. It binds to enhancer sequences and recruits HATs. In Burkitt’s Lymphoma, Myc translocates to a position on chromosomes 2, 14, or 22 near a IgH gene (highly expressed), and Myc therefore also becomes highly expressed. It is a proto-oncogene.
How do DNA Tumor Viruses induce tumorigenesis?
The viral protein sequesters Rb and p53 so the cell proliferation factor (E2F) can transcribe.
What do HPV’s E6 and E7 genes do?
E6 protein product destroys p53, E7 sequesters Rb.
Which cyclin/cdk can phosphorylate Rb?
Cyclins D and E
Name five tumor suppressor genes.
Rb, p53, NF1, APC, BRCA1/2
