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19 Cards in this Set
- Front
- Back
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define transformation
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genetic conversion of a normal cell to a cell that has lost its growth control
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List 6 properties of a transformed cell
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1. change in morphology and growth rate
2. immortalization 3. reduced contact inhibition 4. cahnges in cell-cell adhesion/ anchorage 5.altered gene expression 6. decrease growth factor requirements |
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List the 3 common features of oncogenic viruses
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1. virus infection does not kill teh cell
2. all or some part of the virus' genetic information is stably nherited by the affected cell 3. the virus affects aspectes related to celll growth (proliferation, apoptosis, inhibiton of tumor suppression) |
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Describe the 3 different types of oncogenic retroviruses
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1. transducing virus- encodes its own transformation gene, rapid transformation, highly carcinogenic
2. non-transducing virus-slower transformatino, less efficient 3. long latency viruses- tumorigenesis very rare, very slow |
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How does Rous Sarcoma virus transform cells
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The virus encodes v-src which is not regulated like c-src is. The v-src is a protein tyrosine kinase that phosphorylates and activates other proteins
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What is a defectice/ replication incompetent retrovirus?
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It is a retrovirus that does not encode a pol gene so it cannont replicate itself. The virus must co-infect a cell with a competent virus in order for replication to occur
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How do non-transducing retroviruses cause transformation
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-do NOT encode their own transducing gene
-mechanism of transformation involves alterations in the expression of proto-oncogenes due to nearby integration of a LTR-containing provirus -the host RNA transcripts are promoted from cell sequences but enhanced by viral sequences -example: avain leukosis virus |
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what is the mechanism of transformation by DNA tumor viruses
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DNA tumor viruses force cells into S phase, transformation requires that part of the tumor virus genome integrate into the host genome and become stably inherited (except HPV and EBV which have episomes)
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T/F DNA viruses can transform both permissive and non permissive cells
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false. Only nonpermissive cells are transformed becuase infection of a permissive cell leads viral replication and cell death via lysis
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What is pRb?
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Rb is a regulatory protein that controls cell entry into S phase. Loss or muation of Rb is associated with tumors
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Describe the function of Rb in cell cycle progression
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Rb binds to and inhibits transcription activator E2F which regulates expression of cellular genes that participate in DNA synthesis and cell cycle progression. Rb inactivation drives the cell into S phase.
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Describe how DNA tumor viruses can interfer with Rb and what the result is for the cell
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DNA tumor virus proteins like SV40 LT, HPV E7, or Ad2 EIA bind to Rb and inactivate it. This allows activation of E2F transcription factor which leads to uncontrolled cell cycle progression
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What is the role of p53
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p53 is a highly specific transcription activator that is regulated by mutiple proteins. p53 can cause cell cycle arrest or induce apoptosis if something is wrong with the cell
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How do DNA viruses interfere with p53?
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DNA viruses encode diverse proteins that inactivate or destroy p53 to block the host cell's apoptotic response.
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How does HPV E6 interfere with p53
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E6 binds p53 and ubiquitinates it. p53 is then destroyed by the proteasome
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How does SV40LT interfere with p53
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SV40 LT sequesters p53 and prevents it from being able to act as a transcription factor
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What three proteins are necessary for Epstein-Barr virus transformation
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EBNA-2 a transcripton activator
EBNA-3C a tumor suppressor antagonist LMP-1 a membrane signal transducer |
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What 4 proteins are necessary for KSHV associated transformation
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BCL-2= inhibitor of apoptosis
Kcyclin- G protein coupled receptor FLIP- flice inibitory protein, part of the receptor mediated apoptotic pathway p53/Rb anatgonists |
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Compare how each of these viruses cause transformation
-Transducing retrovirus -Non transducing retrovirus -DNA virus |
transducing retrovirus- transform cells through their oncogenes which are constitutively active proto-oncogenes that promote unregulated cell growth
non-transducing- cause insertional mutagenesis which alters expression of host genes controlling growth DNA-genes force unregualted cell growth and inactivate tumor suppressors |
