Holy week 4 Flashcards
M phase initiator? What are the roles of associated proteins?
Cdk 1 forms initial complex with M-cyclin. Activating phosphorylation by CAK and inhibitory phosphorylation by Wee1. Cdc 25 is phosphatase removing inhibitory phosphorylation. Active M-Cdk then has a positive feedback by inhibiting Wee1 and inducing Cdc 25.
What initiates M1 versus G0?
Growth factors bind tyrosine kinase receptors activating RAS and MAP kinases. Early gene regulatory protein Myc leads to delayed response gene expression (Cdk). Active G1-Cdk inactivates retinoblastoma (Rb) protein making E2F active. Positive feedback then occurs by active S-Cdk on Rbas well as E2F on itself.
Targets of M- CDK?
-Condensins, which facilitate chromosome condensation
-Centrosomal proteins, which increases the number of γ-tubulin nucleating sites and the dynamic behavior
of microtubules, leading to spindle assembly
-Nuclear pore complexes and lamins, facilitating nuclear envelope disassembly
-Proteins associated with Golgi and endoplasmic reticulum, promoting their fragmentation
What are cohesins?
Proteins holding sister chromatids together at kinetochore
What are condensins?
Forms condensed DNA in prophase
What is function of special histone H3 variant CENP-A?
Makes protein complex called kinetochore
What proteins is important for cytokinesis?
Rho organizes actin and and myosin into contractile ring
How is S-phase triggered?
Triggered by G1 Cdk and G1/S Cdk.
What checkpoint does p53 control?
G1 - DNA damage
What checkpoint does ATM/Chk control?
G2 - Inhibits M-Cdk if improperly replicated
What checkpoint does Bub control and how does it stop cell?
Metaphase - misaligned chromosomes
Cohesin protealysis
What are CKIs?
P53 acts as a transcription factor, turning on the expression of genes encoding CKIs (p21). Expression of CKIs arrests the cell cycle, allowing time for the cell to attempt DNA repair. If repair is unsuccessful, p53 then turns on the expression of genes promoting cell death.
How is M-Cdk activity shut off?
Cdk itself activates APC which, in addition to destroying cyclin, also causes anaphase and cytokinesis.
How is G1-Cdk activity shut off?
Short half life and is destroyed without constant growth factor signalling
How is replication prevented from happening more than once?
During G1 phase, initiator proteins bind while Cdk levels are low and they are unphosphorylated. S-Cdk phosphorylates and destroys the initiator proteins like Cdc6 and Cdk levels remain high so that replication cannot occur into the next G1 phase.
Which cell death mechanism is considered a cell survival strategy?
Autophagy
Which cell death mechanism is related to inflammation?
Necrosis
Name 4 morphologiccal features of apoptosis?
- Chromatin condensation
- Plasma membrane blebbing
- Vacuolation of the plasma membrane
- Total cell shinkage and fragmenation
What is a signal for macrophages during apoptosis?
Phosphatidylserines being flipped from cytoplasmic to extracellular side of lipid bilayer.
Explain key features of extrinsic apoptosis
Caused by binding TNF or FAS (cell death receptors). These receptors assemble a scaffolding called DISC which allow autoinduction of caspase 8.
Explain key features of intrinsic apoptosis
Caused by intracellular signs of cell stress/damage. Cytochrome C is released from mitochondria which forms a apoptosome complex capable of inducing autoactivation of caspase 9.
Bax and Bcl-2. What are they involved in and how are they different?
They are present in the mitochondria to regulate mitochondrial membrane permeability and thus apoptosis.
Bax promotes cell death. (P53 increases Bax)
Bcl-2 - suppresses cell death
What are Smac/DIABLO
pro-apoptotic factor (anti-IAP)
What is Bid?
Links extrinsic and intrinsic pathways
Can cell induce apoptosis without caspases?
Yes, either with AIF or endonuclease G.
How does stress such as DNA damage cause cell death?
Transcription factor p53 is increased which leads to increased Bax and decrease Bcl-2. This can lead to cytochrome C release at mitochondrial membrane.
What is autophagy?
Lysosomal degradation of cytoplasmic elements to prolong cell survival.
Morphological features of autophagy
- Encapsulation of intracellular element by membranes
2. Fusion with lysosome to form an autophagosome
What is the reverse Warburg effect?
Tumor cells increase glucose utilization and decrease oxidative phosphorylation. It is thought that the ROS are transmitted to neighboring fibroblast via intercellular communication causing autophagy of fibroblast mitochondria. This releases more pyruvate and lactate for tumor cells.
What is necrosis
Cell “blowing up” resulting in an inflammatory response
