Neoplasm Flashcards
Functions of TP53
It is a tumor suppressor gene.
• cell cycle progression
• dna repair
• apoptosis
• code protein p53
Location of TP53
Chromosome 17p13.1
Mutation of TP53 produces
Li Fraumeni syndrome
Causes of Li Fraumeni syndrome
- increased MDM2 levels ( cause degradation of p53)
- E6 protein of HPV (degradation by transforming proteins of DNA viruses)
- release of p53 by stressed cells by:
🪄 DNA DAMAGE AND HYPOXIA
By protein kinase ATM and ATR
⬇️
Phosphorylation of MDM2 and p53
⬇️
Post translational modifications
⬇️
Separation of p53 and MDM2 bond
🪄 ONCOGENIC STRESS
Activation of oncoproteins
⬇️
Progrowth pathways - MAPK, PI3K/AKT
⬇️
Sustained signalling
⬇️
Increased expression of ARF
⬇️
ARF binds to MDM2 and displaces p53
Functions of p53
Temporary cell cycle arrest
Permanent cell cycle arrest
Apoptosis
Target genes of p53
Genes that cause apoptosis
Genes that cause cell cycle arrest
Genes that induce catabolism / inhibit anabolism
Temporary p53 cell cycle arrest
TP53 ➡️ induce protein GADD45
⬇️ ⬇️
p53 DNA repair
⬇️
CDKN1A gene
⬇️
p21
⬇️
Inhibit CDK4 and D cyclins
⬇️
Inhibit progression from G1 to S
Pro apoptotic genes and pathway involved im p53 induced apoptosis
BAX, PUMA
intrinsic
APC (adenomatous polyposis coli) is located on chromosome?
5q21
Loss of function mutation of APC causes
Familial adenomatous polyposis
Autosomal dominant
Later produces colom cancer
Beta catenin binds with ________ to maintain contact inhibition
E cadherin - protein that maintains intercellular adhesion
During injury they separate, catenin enters nucleus to stimulate genes for cell repair and join with cadherin once done.
Loss of contact inhibition or loss of E cadherin causes metastasis and invasion of tumor.
Loss of function mutation of CDH1 produces
Familial gastric carcinoma
Because CDH1 is associated with E cadherin gene
Proteins coded by CDKN2A
P14 - activate p53 pathway (oncogenic stress)
P16 - inhibits CDK4 / cyclin dependent kinase phosphorylatiom of RB
Mutation of CDKN2A - familial carcinoma
Melanoma
Mutation of CDKN2A - sporadic
Bladder
Head and neck
Acute lymphoblastic leukemia
TGF- ɓ pathway
NORMAL
Bind to receptors
⬇️
Stimulate intracellular signals
⬇️
Induce transcriptional regulator
⬇️
Activate SMAD protein
⬇️
Activate anti proliferative genes
Protein related to TGF ɓ pathway
SMAD
Type of mutation in TFG ɓ pathway
Loss of function
TGF ɓ mutation cancers
T - sTomach
G - colon
Fuck - endometrium
Mutational inactivation of SMAD causes
Pancreatic cancer
PTEN full form
Phosphatase and tensin homologue
PTEN gene code
10q23
Mutation of 10q23 (PTEN)
Cowden syndrome
Frequent benign growths like skin cancer, breast, endometrium, thyroid tumors
PTEN acts on
PI3K/AKT pathway
