20.3 Tumor Suppressor Genes Flashcards
act oppositely to oncogenes; inhibit cell proliferation and tumor development
tumor suppressor genes
the first tumor suppressor gene identified, ()
Rb
inherited mutation in Rb + a second somatic mutation resulted in the loss of the normal Rb allele → ()
development of retinoblastoma
Rb serves as a () → loss of Rb gene leads to tumor development
negative regulator
() was the second tumor suppressor protein identified
p53
loss of p53 interferes with ()
induction of apoptosis
summarize the normal function of p53
acts in response to DNA damage → induction of p53 activates transcription of proapoptotic and cell cycle inhibitory genes
p53 activates the CKI (1), as well as the proapoptotic Bcl-2 family members (2)
- p21
- PUMA and Noxa
loss of p53 interferes with induction of apoptosis, caused by the oncogene protein ()
MDM2
() tumor suppressor gene encodes a lipid phosphatase the dephosphorylates PIP3
PTEN
summarize the function of PTEN as a tumor suppressor gene involved in signal transduction
PTEN inhibits PI3K and Akt → leads to inhibition of cell survival and cell proliferation; acts oppositely to PI3K
tumor suppressor gene () encodes for p16, which is a CKI that works to inhibit Cdk4,6/cycD complexes
INK4
summarize the function INK4 as a tumor suppressor gene involved in cell cycle progression
- INK4 encodes for p16, which in turn inhibits Cdk4,6/cycD complexes
- inhibition of Cdk4,6/cycD complexes leads to decreased inhibition of Rb
- mutational inactivation of Rb removes a key negative regulator of the cell cycle
function to maintain the integrity of the genome
stability genes
examples of stability genes
- BRCA1
- BRCA2
- ATM gene
how do stability genes act as tumor suppressor genes
they prevent high mutation frequency in oncogenes or tumor suppressor genes
genes coding for microRNAs (miRNAs) can act as tumor suppressor genes because ()
miRNAs serve as major regulators of gene expression in eukaryotes
in general, miRNA expression in tumors is ()
low
let-7 miRNA acts as a tumor suppressor by ()
silencing the expression of the oncogenes rasK and c-myc
() acts as a tumor suppressor by silencing the expression of the oncogenes rasK and c-myc
let-7 miRNA
large number of different mutations in tumor affect a small number of complementary pathways that regulate:
- cell fate
- cell survival
- genome maintenance
mutations in the ff pathways affect cell survival
- cell cycle/apoptosis
- RAS
- PI 3-kinase
- STAT
- MAPK
- TGF-beta
mutations in the ff pathways affect cell fate
- Notch
- Hedgehog
- APC
- chromatin modification
- transcriptional regulation