Micro Test 4: Viruses & Cancer

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BrookeNH10
ID:
198424
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Micro Test 4: Viruses & Cancer
Updated:
2013-02-06 14:43:41
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Micro Test Viruses Cancer
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Micro Test 4 Viruses & Cancer
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  1. In cancer, you lose regulation of
    stem cells (this is the one thing that is almost universally common to all cancers)
  2. Binding keeps cell cycle off
    E2F
  3. RB, p300
    Promote binding of E2F (keeps cell cycle off)
  4. Rb, p300 are what phases of the cell cycle
    Stop cells btw G1 and S
  5. In presence of DNA damage, turns cell cycle off
    p53
  6. Multiple signals control gene transcription and the cell cycle
  7. Most cancer cells have
    Mutiple mutations and are aneuploid (have a variable # of chromosomes)
  8. Name 6 viruses associated with cancer
    • HPV
    • HBV
    • HCV
    • HTLV-1
    • EBV
    • HHV8/KSHV
  9. Cancer associated with HPV
    • Cervical Cancer
    • Small, nuclear replicating dsDNA virus
  10. Cancer associated with HBV
    • Hepatocellular carcinoma
    • Small, nucear localized retroid virus
  11. Cancer associated with HCV
    • Hepatocellular Carcinoma
    • +ssRNA virus
  12. Cancer associated with HTLV-1
    • T cell leukemia
    • Retrovirus
  13. Cancer associated with EBV
    • Burkitt's Lymphoma, Nasopharyngeal Carcinoma
    • Large dsDNA virus
  14. Cancer associated w/ HHV8/KSHV
    • Kaposi's Sarcoma, plasmablastic multicentric Castleman's disease
    • Large dsDNA virus
  15. 2 Viruses inplicated in BrCA
    EBV, high risk HPV
  16. Two proteins HPV have that when inactivated cause cancer
    • E6- inactivates p53
    • E7- inactivates Rb
  17. Inactivates p53
    E6
  18. Inactivates Rb
    E7
  19. Cancer generally occurs when virus is integrated into host genome.
    E2 expression=
    E6 & E7 expression=
    • E2 expression is shut-off
    • E6 and E7 are no longer regulated

    • Leads to unregulated cellular replication
    • Dead end for virus
  20. Controls proliferation via E2F
    Rb
  21. 3 Rb homologues
    pRb, p107, p130

    pRb is the main target of HPV E7, Ad E2, SV40 T
  22. Releases E2f
    phosphoRB
  23. Proliferation signals including _____ and _____ cause pRb to release E2F
    • transduction cascades
    • Kinase activation
  24. E2Fs stimulate
    transcription

    • "early phase" genes
    • Required for DNA synthesis, cell growth
    • Also involved in differentiation
  25. 4 E2F homologues known
    • E2F-1,2,3,4
    • E2F-1 is most critical for proliferation
  26. Most common mutations found in cancer cells
    p53
  27. Binds to damaged DNA and activates mismatch repair, Inhibits S/G2 transition, or induces apoptosis
    p53
  28. p53 inhibits cells from moving to what phase of the cell cycle
    S to G2
  29. Weakly transforming protein of HBV
    HBx protein
  30. HBx's global effects on transcription
    • Interacts w/ numerous transcription factors
    • Alters histone acetylation (activates p300, inhibits HDAC)
    • Alters DNA methylation at selected promoters
  31. HBV Cancer caused by (2 things)
    • Integration into host DNA (downregulates some critical host genes, upregulates others)
    • HBx protein, which is weakly transforming
  32. Name 3 transcriptional factors HBx activates
    • c-myc
    • AP-1
    • NF-kB
  33. Acetylation of histones: 
    Enzyme?
    Activates or represses DNA transcription?
    • HATs (Histone Acetyl Transferase)
    • Activates DNA transcription
  34. Deacetylation of histones:
    Enzyme?
    Activates or represses DNA transcription?
    • HDACs (Histone Deacetylase)
    • Unacetylated histones bind DNA tightly, repressing transcription
  35. Mechanism by which HCV causes cancer
    • HCV chronically activates infected cells
    • Liver undergoes repeated rounds of damage from immune system

    NO evidence of HCV integration, since HCV doesn't replicate via DNA
  36. Burkitt's lymphoma is found
    Equatorial Africa, Papua Niu Gini
  37. Burkitt's Lymphoma:
    Associated with what virus?
    Transformation of what?
    • EBV
    • B cells
  38. Transient benign infection of B cells?  Associated with what virus?
    • Infectious mononucleosis
    • Benign infxn of B cells
  39. Primary site of EBV infxn
    Oropharyngeal epithelium
  40. Immortalize B cells in vitro (EBV oncogenesis)
    EBNA-2, LMP-1, -2
  41. Suppress innate immunity via Rig-I (EBV oncogenesis)
    EBER-1,-2
  42. Can B cells infected with EBV continue to differentiate
    Yes

    EBV can also become latent in B cells (express EBNA-1)
  43. When B cells contain latent EBV, they express?
    This protein does?
    EBNA-1

    • Inhibits Ag processing
    • Prevents CTL killing
  44. Translocation present in 95% of Burkitt Lymphoma
    IgH/c-Myc translocation
  45. Subverts intracellular signaling
    EBV
  46. Progenitor Cell of Sporadic EBV and Burkitt's Lymphoma

    Progenitor Cell of Endemic and HIV-associated EBV
    Germ Center B cell

    GC, late GC or memory B cell
  47. EBV and Burkitt lymphoma Ig gene breakpoint:
    Endemic?
    Sporadic?
    HIV-associated?
    • Endemic- J region, S-mu region
    • Sporadic- J region, S-mu region, S-alpha region
    • HIV- associated- S-mu region
  48. Myc translocation and BL:
    Found in most (all?) BL
    • IgH= 80%
    • IgL= 20% (equally distributed btw Vk and Vl loci)
  49. Gene contains sequences similar to Ig switch regions
    Myc gene
  50. Translocation of Myc genes occurs due to
    Inappropriate RAG or switch recombination in EBV-infected GC B-cells

    Places Myc downstream of strong B cell promoter
  51. Excess Myc usually leads to death by
    p53-dependent apoptosis
  52. Type of Burkitt Lymphoma that expresses wild type Myc
    Endemic BL
  53. Type of Burkitt Lymphoma that expresses Ig:Myc fusion
    Sporadic and HIV-associated
  54. Myc activates
    S-phase
  55. KSHV/HHV transforms what type of cells
    Endothelial cells
  56. HHV8 transformation of endothelial cells leads to
    • Chromosome instability
    • Alteration of cellular gene expression
    • Acquisition of telomerase activity
    • Anchorage-independent growth
    • Increase in cell invasiveness
  57. Name 8 KSHV oncogenes
    • LANA
    • K13/vFLIP
    • Kaposin A
    • Kaposin B
    • K1
    • vGPCR
    • vIL6
    • vIRF-1

    If you have time go back an learn what these do (slide 29)
  58. First identified human retrovirus.  It also causes cancer
    HTLV-1
  59. 2 things HTLV-1 can cause
    • Adult T-cell leukemia/lymphoma (ATL)
    • Tropical Spastic Paraparesis/ HTLV-associated myelopathy (TSP/HAM)
  60. Name 2 HTLV-1 oncogenes
    • TAX (p40)
    • HBZ (HTLV-1 bZIP)
  61. HTLV-1 oncogenes that activates D-type cyclins and cyclin-dependent kinases
    TAX
  62. Mutations in important ______ are often found in virus-derived cancers
    host genes
  63. Can result from manipulation of cell proliferation by viral genes
    Hyperplasia
  64. Cell cycle moves from G0/G1 to S phase
    Leads to upregulation of E2F-dependent genes
    Rb
  65. Cell cycle moves from S to G2-phase even in the presence of damaged DNA
    p53
  66. Name 3 viruses that evade apoptosis and killing by innate immunity
    • HPV- E6 blocks p53 signaling
    • HHV8- K13/vFLIP inhibits caspase activation
    • EBV- EBER-1 suppresses Rig-1
  67. Name a virus that evades T-cell killing by reducing antigen presentation
    EBV- EBNA-1 interferes with antigen processing by proteasomes

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