Rb-1 Anti-oncogene Flashcards
Rb-1
Anti-oncogene essential for normal development
Acts through protein-protein interactions with TF E2F
Binds to E2F and inhibits transcription of GPG
-by HDAC and HMT —> closed chromatin structure
Normal cell: Rb1 is phosphorylated (no interaction with E2F)
E2F
Stimulates growth promoting genes (c-myc)
Uncontrolled growth of GPG if
Rb1 gene deleted
Rb1 binds an oncogene —> releasing it from E2F
Rb1 and polymerase interactions
Pol 1 TF —> prevents mediated transcription of rRNA
Pol 2 TF E2F —> blocks transcription of pol II dependent genes
Pol III TF TFIIIB —> blocks tRNA and 5S rRNA transcription
Interaction of p53 and Rb1
Through p21 (CDK) keeps Rb1 unphosphorylated - inhibits Cell growth
Some leukemias
Deletion of chromosome 13 and loss of miRNA genes = cancer
Some ovarian cancers
miRNAs are down regulated (due to closed chromatin structure)
Altered miRNA transcription
Transcription activated by p53 and repressed by c-myc