Cell Cycle, Apoptosis and Cancer Flashcards
What are the stages of the cell cycle?
Mitosis- nuclear division
Interphase- G1, S and G2
G0 phase- withdraw from cell cycle
What is G1 phase>
Gap 1 phase- RNA and protein synthesis needed for DNA replication
What is the S phase?
Phase of DNA synthesis
What is G2 phase?
Gap 2 phase- DNA stability is checked
Restriction point
Occurs in G1- Cell must receive growth factors to move past restriction point. Occurs about 2 hours prior to S phase.
G1 checkpoint
occurs around the same time of restriction point- Occurs in response to DNA damage before replication
G2 checkpoint
Verify the completion of genomic duplication
Metaphase checkpoint
Ensures that the chromosomes are attached to mitotic spindles for proper separation
Cell proliferation
Myc-TF will increase gene expression of G1 cyclin dependent kinase- CDK then phosphorylates retinoblastoma, releasing the E2F protein.
What is the factor that drives G1 to S phase?
The release of E2F from phosphorylated Rb will begin s phase gene transcription
What genes do E2F stimulate?
Transcription of Cyclin E and Cyclin A which activates CDK2
Feedback of cell proliferation
Cyclin E-CDK2 and Cyclin A-CDK2 keep Rb in hyperphosphorylated state. Transcription of genes also create a positive feedback loop
Activation of cyclin-CDK activity
Cyclin binds to CDK which partial activates the t loop but full activation requires CDK-activating Kinase to phorphorylate the t-loop
What cyclin-CDK complexes get past restriction point?
Cyclin D- CDK4 and Cyclin D-CDK6
Inhibition of cyclin-CDK activity
Wee1 kinase inhibits by phosphorylating “roof site” of complex
p27 will bind to both cyclin and CDK to inactivate the complex
What is the function of cdc25 phosphatase?
It will dephosphorylate roof site after Wee1 inactivates CDK complex
What is APC/C?
Anaphase-promoting complex- a member of the ubiquitin ligase family. it regulates the progression from metaphase to anaphase.
What is ubiquitin?
a small protein that is attached to the lysine residues of proteins to signal destruction of the protein
How does the cell cycle move into anaphase?
CDC20 will activate APC/C leads to the addition of polyubiquitin to S and M cyclins. The destruction of cyclins inactivates the CDK and allows for progression into anaphase.
what is p53?
The guardian of the genome- responds to DNA damage and will regulate transcription to halt cell cycle
What is the process for activation of p53?
DNA damage will activate protein kinase. p53 will then be phosphorylated and begin transcription of genes for p21
What is p21?
It is a cyclin-dependent kinase inhibitor (CKI) and will primarily inhibit CDK2
What is the intrinsic pathway of apoptosis?
Mitochondrial dependent- responds to DNA damage, lack of O2, nutrients or extracellular survival signals
What is the extrinsic pathway of apoptosis?
It is a mitochondrial independent cycle
Capase activation
Capase are responsible for apoptosis. Activated by protease cleavage. Will make a heterodimer that forms from a small and a large subunit
What are the two initiator proteins of apoptosis?
Capase 8 and capase 9
What are the executioner proteins of apoptosis?
Destroys the targets and executes apoptosis. Ex is Capase 3, 6 and 7- They are activated by capase 8 and 9
Describe the intrinsic pathway of apoptosis
Capase 8 is activated which will then stimulate BAX. BAX then aggregates in the mitochondrial membrane, releasing cytochrome C into the cytosol. Cyto C and hydrolysis of ATP activates Apaf1 creating an apoptosome. This then recruits and activates procapase 9 leading to the activation of executioner proteins.
What is a proto-oncogene?
Growth factors, receptors of GFs, transcription factors and signal transducers- Most are involved in cell growth and division
What is an oncogene?
a mutation in a proto-oncogene that results in increased expression of proteins and causes the cell to act abnormally. Most result in cancer mutations
What is the HER2 gene?
Tyrosine Kinase Receptor. Mutation causes overexpression of HER2, seen in many breast cancers
Tumor suppressor examples
RB1- causes retinoblastomas
TP53
PTEN- phosphatase and tensin homolog- prostate cancer
APC- Adenomatous polyposis coli- Colon cancer
What is Herceptin?
An inhibitor of oncoproteins- HER2
What is Gleevec?
An inhibitor of oncoproteins- BCR-ABL
What is Erbitux?
An inhibitor of oncoproteins- EGF receptors