Cancer genes

Cancer genes：Burkitt’s Lymphoma、Cancer requirement、Stability genes、proto-oncogenes……

Cancer genes

• tumor suppressor genes
  • suppressor
    • when mutate, they allow malignency develop
    • one copy is enough to suppress, so both genes need to be loss to develop malignancy
      • but one copy for whole people is really risk for cirtain cancer development
        • Rb single mutation cause Retino blastoma susceptibility
  • p53
    • transcription factor p53
      • monitor DNA integrity in G1 check points of cell division
        • if DNA damages detected
          • p53 halts cell division and activates DNA repair enzymes
            • DNA is successful repaired
              • p53 allow cell cycle continue
            • if damage is irreparable
              • p53 directs appoptosis
      • phosphorylated p53 is active functioning
      • MRN binds double-strand break in DNA then recruits and activates kinases ATM, ATR.
        • ATM and ATR phosphorylate and activate p53
    • mutated in 40% of all cancers
  • Rb
    • Rb protein
      • in pocket protein family
        • a binding pocket for other proteins
      • dephosphorylated state
        • binds transcription factor E2F
      • phosphorylation state
        • releases E2F
          • transcription factor of Cdc2, G1 cyclins
            • proteins neccessary to pass through G1/S check point
          • transcription factor for enzymes of DNA replication
        • can be phosphorylated by cycline E binded CDK2
          • p21 binds and inhibits cyclineE-CDK2's kinase activity
            • transcription factor p53 increases p21's gene expression
      • its phosphorylation state allow cell to pass G1/S check point
• proto-oncogenes
  • amipilficator
    • when mutates, they direct cause malignency
    • most by "permenent on" mechanism
      • needs only one copy of those genes
  • Growth factors, or mitogens
  • Receptor tyrosine kinases
    • encode receptors for growth factors
      • PDGF receptors
      • EGF receptors
    • ERB proto-oncogenes
      • normal
        • EGF(epidermal growth factor) binds EGF binding domain and activates tyrosine kinase domain's activity
      • mutated ErbB oncogene
        • lose EGF binding domain
        • constant actibated tyrosine kinase domain
  • Cytoplasmic tyrosine kinases
    • Kinases
      • Src kinase
        • activated by 2%-5% or all cancers
  • Cytoplasmic Serine/threonine kinases and their regulatory subunits
  • Regulatory GTPases
    • encode signaling transduction proteins under growth factor pathways
      • protein rely swiches
        • Ras protein
          • activated by 20%-30% of all cancers
  • Transcription factors
• Stability genes
• Retrovirus cause cancer
  • By viral genome Itegration
    • insertion might cause mutation in host genome
      • insertional mutagenesis
      • may inactivates an tumor suppressive gene
    • Non-acute transforming retrovirus
      • viral LTRs contain promotor/ enhancer
        • viral LTRs contain transcription regulatory elements to increase cellular proto-oncogene level
        • retrovirus LTRs contain promoters, enhancers, or transcription termination sequence
    • acute transforming retrovirus
      • viral carries oncogenes
        • cellular proto-oncogenes may addes or substitutes into viral genome
        • The oncogene most replace one viral gene and make virus replicate defective
          • Those virus require a competent helper virus' help
    • Trans-acting retroviruses
      • viral contains accessory gene products that can transform cells
        • not cellular oncogenes
        • but normal viral genes that evade cellular defence
          • stop appoptosis by block some tumor suppressor genes:p53/Rb
        • usually 1-2
  • some virology definations
    • transformation
      • means the induction of malignancy by retrovirus
• Cancer requirement
  • Uncontroled cell cycle
  • multisteps genetic changes
    • first usually induced by viruses
• Burkitt’s Lymphoma
  • c-myc translocated from chromosome 8 to chromosome 14
  • results in the c-myc gene being placed next to an enhancer of an immunoglobulin gene
  • Can be facilitated by EBV?