slides6spring08 - Genetics - PCB 3063 Our Final Focus:...

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Genetics - PCB 3063 Our Final Focus: Genomic Change and the Consequences of Genomic Change Cancer and Oncogenes
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Genes and Cancer There are four main classes of oncogenes , based upon the products they encode: Growth factors - sis and erb B GTP-binding proteins - ras Protein kinases - src , abl and raf Transcription factors - myc , fos and jun The potential for growth factors to stimulate growth should be obvious - they typically act in an autocrine fashion in cancers. Protein kinases and GTP-binding proteins (aka G-proteins ) act to transmit signals from the outside the cell to the nucleus. Transcription factors can act as oncogenes when they regulate genes involved in growth control.
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Cancer and Retroviruses Oncogenes were originally discovered because they are present in some retroviral genomes. Retroviruses are RNA viruses that encode a reverse transcriptase . – Reverse transcriptase copies the RNA genome, generating a DNA molecule (ultimately double stranded) that is integrated into the host genome as a provirus : gag , pol , and env genes are found in all retroviruses. – But the cancer causing retroviruses also carry an onc gene.
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Oncogenes were originally discovered because they are present in some retroviral genomes. – Proviruses have long terminal repeats (LTRs) which act as transcriptional promoters. – Proviral transcripts encode products necessary for viral RNA packaging - retroviruses reproduce through transcription. – Some retroviruses have v- onc genes that act to stimulate cellular growth - presumably to the advantage of the virus. Acutely transforming retroviruses have the v- onc gene in their genome at the time of infection while non-acutely transforming retroviruses acquire a v- onc gene by recombination. Cancer and Retroviruses
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Cancer and DNA Viruses • Some DNA viruses also transform cells. – These viruses include SV40 and HPV (human papiloma virus). • SV40 is a polyomavirus that transforms cells through the activity of the T-antigens: SV40 T-antigens are formed by alternative splicing. T-antigens are multifunctional, proteins that can inhibit tumor suppressors .
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Cancer and DNA Viruses •S V 4 0 i s a polyomavirus . – Polyomaviruses pack 6 genes into 5 kb , and they require host cell entry into S phase . – Polyomaviruses enter the nucleus and uncoat, replicate, and then they assemble in the nucleus. An unknown proportion of polio vaccine lots were contaminated with SV40 - a cancer risk in humans? Probably not - see Shah (2007) Int J Cancer 120: 215-223. T-antigen activities are also regulated by phosphorylation
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• Some HPV (human papilomavirus) strains transform cells : Gene: Function: E1 Initiation of DNA replication (helicase) E2 Transcriptional regulation/DNA replication E3 Unknown E4 Disrupts cytoskeleton?
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This note was uploaded on 04/17/2008 for the course PCB 3063 taught by Professor Marta during the Spring '08 term at University of Florida.

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slides6spring08 - Genetics - PCB 3063 Our Final Focus:...

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