Cell Cycle, Apoptosis, And Cancer Flashcards
What happens in S phase
DNA synthesis/replication
Histone syntheisis
Centrosome formed
Chromosome duplication
What happens in M Phase
Mitosis (PMAT)
- chromosome duplication/segregation
- cytokinesis
What happens in G1 phase of interphase ?
RNA and protein synthesis needed for DNA replication
*no cell division
What happens in G2 phase of interphase ?
DNA stability is checked
*prep for mitosis
What happens in G0 stage of the cell cycle?
Nothing. No division occurs.
What drives cell proliferation in cell signaling networks
Myc-TF
Myc is a gene regulatory protein
Myc increases _________ levels in the cell to drive proliferation
G1-Cyclin-dependent kinase (CDK) levels
CDK phosphorylates what in cell cycle that drives cell proliferation
Retinoblastoma (Rb)
Phospho-Rb (created from CDK) releases what in cell signaling that drives cell proliferation
Releases sequestered E2F (elongation factor)
*phophorylated RB is “inactive”. It releases the E2F protein to go on in its active form
Binding of Cyclin to CDK only causes partial activation of CDK. What is needed for full activation of CDK?
CDK-activating kinase (CAK)
*adds phosphate to T-loop “cave site”
What are the CDK inhibitors (CKI) that inhibit cyclin-CDK complex?
WEE1
- phosphorylate CDK complex inactive by added phosphate to the “roof site”
P27 (KIP1)
-bind to attached CDK complex (both the cyclin and CDK) and make it inactive
What opposes WEE1 inhibition of the CDK complex ?
CDC25 phosphatase
- removes the phosphate attached by WEE1 kinase to make it active again
- dephosphorylates the “roof site”
APC/C is activated by binding to _____
CDC20
*starts ubiquitination pathway
The Activated APC/C poly-ubiquitinates it substrates. What are two proteins ubiquitnated by APC/C in the cell cycle? And why does this proteins need to be down regulated?
S- and M- cyclin proteins
**cyclin-S and cyclin-M activity must be inhibited to move the cell into anaphase. Without the cyclins the CDK is inactivated.
**both S- and M- proteins are sent to proteasome to get degraded
What E3 ubiquitin ligase keeps P53 inactive though degradation in quiescent cells ?
MDM2
DNA damage (increases or decreases) protein kinase activity?
Increases
*protein kinase phosphorylates P53 to make it active
Activation of P53 leads to (increased or decreased) transcription of specific CKI (P21).
What is the effect on the cell cycle?
Increased
*binding and inactivation of cyclin-CDK by P21 causes cell cycle arrest
What hyperphosphorylates RB to make it inactive to release active E2F?
CyclinD-CDK 4 and 6 complex’s
*which helps the cells pass though the restriction point in G1
Briefly describe the extrinsic pathway of cell apoptosis.
*mitochondrial-independent pathway
- A Fas ligand and TNFa binds to Fas receptor and TNFa receptor on the outside of the cell
- FADD complex will activate production of Procaspase-8
- TRADD complex will stimulate activiation of procaspase-8 to caspase-8
- Caspase-8 will activate procaspase 3,6,7 to caspase 3,6,7.
- Active caspase 3,6,7 will initiate apoptosis
Briefly describe the intrinsic pathway of apoptosis.
*mitochondrial dependent because relied on cytochrome C
- DNA damage activates P53
- Active Caspase 8 will convert Bid to tBid and activate BAX and BAK
- P53, BAX, BAK stimulate release of cytochrome C from the mitochondria
- APAf-1 adds cytochrome C to an apoptosome
- The Apoptosome activate procaspase 9 to caspase 9
- Caspase 9 activates procaspase 3, 6, 7 to caspase 3, 6,7
- Caspase 3, 6,7 signal apoptosis
**BCL-2 inhibits release of cytochrome C from mitochondria and the function of APAF-1