Lecture 9 Flashcards
Retinoblastoma
Cancer of the retinoblast (genes of the eyes)
Types:
Familial: inherit one bad gene, get 2nd bad RB gene via somatic mutation or LOH
Sporadic: get 1st bad gene via somatic mutation, get 2nd via somatic mutation or LOH
Cell Fusion Experiments
Learned that some tumor forming genes are dominant (oncogenes) and some are recessive (tumor suppressor genes)
Rb Protein pt. I
Properties: 105kDa, phosphoprotein, its phosphorylation varies throughout the cell cycle
Interaction with DNA Tumor Viruses: E1A, E7, and large T antigen bind to Rb protein and block its function
Rb Protein pt. II
Function: to bind E2F transcription factor and prevent E2F from binding to DNA
Function regulation: hypophosphorylated Rb binds E2F while hyperphosphorylated Rb releases E2F
CDK4/6
Hypophosphorylates Rb
Regulated by Cyclin D levels
CDK2
Hyperphosphorylates Rb
Regulated by Cyclin E levels
P(INK48)
Inhibits CDK4/6 activity and slows hypophosphorylation of Rb proteins
Binds TGIF-B to its receptor on cell surface, increasing expression of P(INK48)
Cell Cycle Clock Regulation Disruption
Deletion of Rb protein
Deletion of P(INK48)
Over expression of E2F
Infection with HPV