Cell Cycle, Apoptosis, Cancer Flashcards
Role of different phases in Cell cycle
G0: no cell division
G1:
Cell growth
RNA and protein synthesis
S Phase: Histone synthesis Centrosome formed Chromosome duplication DNA Replication
G2:
Preparation of mitosis
M Phase:
Mitosis
Check points (4)
1) Restriction Point
- make sure that there are enough GROWTH FACTORS before S phase
2) G1 Phase
- make sure DNA is not damaged before S phase
3) G2 Phase
- make sure DNA duplication is proper before M phase
4) M Phase
- make sure mitotic spindle and chromosome aligned and attached
Activation of E2F protein
signal molecule (mitogen) to mitogen receptor- > ras -> MAP kinase-> myc -> cyclin D (CDK 4 and CDK 6 in G1 phase) complex activated-> phosphorylate RB to take it off of E2F-> active E2F release
G1- S phase cell signalisn
active RB bind to inactive E2F-> active g1-cdk hyperphosphorylates rb to make inactive-> E2F off and active-> activate cyclin E and A-> activate cdk2 (s phase) ( positive feedbacak to rb-> DNA synthesis
Hyper/Hypo phosphorylation activity of Rb
Hyperphosphorylation of Rb= inactive= allows g1/s transition
hypophosphorylation of RB= active= block g1/s transition
Metaphase to Anaphase activity
APC/C inactive (ubiquitin ligase)-> bind to cyt c to activate-> add polyubiquitin chain to S and M cyclin (cyclin a and B)-> marked for degradation by proteosome-> inactive CDK
Regulation of CDK activity with Wee1 and Cdc25
Wee1 inactivates CDK-cyclin complex by adding P to roof site
Cdc25 phosphatase activate CDK-cyclin but taking away P from roof site
CAK affect cave site
p21 leads to
p21 binding will inactivate cyclin-cdk complex for g1/S transition (Cyclin e- cdk2) and p phase (cyclin A-cdk2).
Rb will be hyperphosphorylated (active) and sequester E2F
Intrinsic Pathway of Apoptosis factor
MITOCHONDRIAL DEPENDENT
injury, DNA damage, lack of oxygen, lack of nutrient, lack of extracellular survival signals (mitochondrial dysfunction) (BAX/ BLC2 key regulator)
Oncogene Her2
Val to Gln mutation
RTK will be continuously active
Oncogene EGF
deletion
RTK continuously active
glioblastoma
Oncogene BCR-ABL
expression
chromic myelogenous leukemia
Tumor Suppressor Gene
arrest cell cycle in Active form and promote apoptosis (Rb)
when mutated- rb hyperphosphorylated constantly and continue cell progression
Metastasis Suppressor Function
Cell Adhesion Protein
- prevent tumor cells from dispersing
- block loss of contact inhibition
Stages of cancer
normal epithelium- > hyper proliferative epithelium -> early adenoma -> intermediate adenoma-> late adenoma-> carcinoma- > metastasis
loss of apc- normal to hyper
activation of ras- early to inter
loss of tumor suppressor gene - inter to late
loss of p3 - late to carcinoma
