04a: Cell Cycle and Apoptosis Flashcards
Give examples of adult cells that don’t undergo proliferation.
Nerve, striated muscle, cardiomyocytes
Give examples of adult cells that undergo frequent proliferation.
Fibroblasts, Bone marrow, Myeloid
A non-dividing cell is in (X) phase.
X = Go
Following the appropriate stimulus, cell enters cycle of division and proceeds through which phases (in order).
- G1
- S
- G2
- Mitosis
Cell undergoes (X) in G1.
X = Growth and metabolism
Cell undergoes (X) in S.
X = DNA replication
Cell undergoes (X) in G2.
X = Preparation for division
Chromosome number in G1.
2n (diploid)
Chromosome number in S.
2n to 4n
Chromosome number in G2.
4n
Chromosome number in M.
4n to 2n
Condensing chromosomes indicate (interphase/prophase).
Prophase
Anaphase in mitosis involves separation of:
two sister chromatids
Give examples of cells that skip certain cell cycle phases. Which phase(s) does each skip?
- Megakaryocyte (late anaphase and cytokinesis)
2. Trophoblast (late anaphase and cytokinesis)
(X) cells have abnormal, uneven segregation of chromosomes, resulting in (haploid, polyploid, uneuploid) cells.
X = cancer
Uneuploid
Disease associated with (X) cause reduction in reduced platelet counts?
X = decreased polyploidy in megakaryocytes
Cyclin D peaks primarily in which phase?
G1
Cyclin E peaks primarily in which phase?
S
Cyclin A peaks primarily in which phase?
S (and a bit into G2)
Cyclin B peaks primarily in which phase?
Late G2, and into M
Which proteins are important for entrance/transitions into/out of cell cycle phases?
Cyclins
Cyclin forms an active complex when coupled with:
CDK (cyclin-dependent kinase)
What are CKIs? List examples.
CDK inhibitors
p16, p21, p27
CKIs inhibit which specific reaction?
Phosphorylation by active Cyclin-CDK complex
High levels p16 effect on cell cycle.
Inhibits Cyclin D (coupled with CDK 4 or 6); so stops cell from entering G1 phase
High levels of p21 effect on cell cycle.
Inhibits Cyclin E (coupled with CDK 2); halts cycle
High levels of p27 effect on cell cycle.
Inhibits Cyclin E or A (coupled with CDK 2); halts cycle
Whats the function of the CDC2-Cyclin B complex?
Activates proteins on the chromosomes that are responsible for chromosome segregation.
What’s the primary control mechanism for CKIs?
Transcription regulation
Rb is known as a(n):
Tumor suppressor
Free E2F function:
Activates genes that regulate DNA synthesis
E2F, bound to (X), function:
X = Rb
Function (activates genes for DNA synthesis) is suppressed
CDK-cyclins affect (Rb/E2F) in which way(s)?
Affect both! Directly phosphorylate Rb, so can’t bind E2F. This allows E2F to carry out function of gene activation (cell cycle proceeds)
CKI affect (Rb/E2F) in which way(s)?
Indirectly allow cell cycle arrest by inhibiting Cyclin-CDK complex from phosphorylating Rb.
Necrotic cell death involves (X) and occurs as result of (Y).
X = lysis of membrane and release of cell content
Y = trauma or infection
Apoptosis is result of (X) activation by (Y) signals.
X = caspases Y = intracellular biochemical signals
Caspases are specifically (X) enzymes, so they act to:
X = cysteine protease
Hydrolyze specific peptide bonds
Caspases are initially produced as:
Inactive pro-caspases
What initial step allows activation of the caspase cascade?
Pro-caspases (8, 9, 10) are autocatalytic, so cleave themselves to produce active caspases
Active caspases 8-10 act on:
Caspases 3, 6, 7 (cleave them)
Active Caspases 3, 6, 7 act on:
Other cellular proteins
An apoptotic cell undergoes changes in which structure(s)?
- Plasma membrane
- Cytoskeleton
- Nuclear DNA (fragmentation)
In apoptotic cell, degradation of chromosomal DNA is carried out by:
Endonucleases (caspase-activated DNase)
Fate of remains of apoptotic cell
Uptaken and digested by macrophages
What are the main pathways to apoptosis?
- Death receptor pathway
2. Mitochondrial pathway
Whats TNF-a?
Death ligand that, upon binding death receptor, initiates apoptosis via death receptor path
List steps that initiate death receptor pathway.
- TNF-a binds Fas death receptor
- Intracellular adaptor protein (FADD) binds to cytoplasmic side of death receptor
- Recruits pro-caspase (8-10), which undergo autocatalytic activity and initiate caspase cascade
Under normal conditions, cytochrome C is present in/on:
In mitochondrial intermembrane space
Under apoptotic conditions, cytochrome C is present in/on:
Translocated to cytosol via pores
Upon leaving mitochondria, cytochrome c:
Binds Apaf1 and pro-caspase 9, forming apoptosome
What’s the apoptosome?
Complex of:
- Cytochrome c
- Apaf1
- Pro-caspase 9
What regulates Cytochrome C release from mitochondrion?
Channels (Bcl proteins)
Bcl proteins are divided into (X). List examples of each.
X =
- Anti-apoptotic: Bcl-2 and Bcl XL
- Pro-apoptotic: Bax and Bak
Bcl-2 activity has what effect on Cytochrome C movement?
Prevent formation of membrane pores through which Cytochrome C would leave mitochondria
The mitochondrial membrane pores are composed of:
Dimers or polymers of Bax and Bak
List some facilitators of Bax and Bak. What effect do these have on apoptosis?
Bid, Bad, Noxa
Promote apoptosis
T/F: the presence of Bax/Bak facilitators determines cell death or survival.
False - ratio between anti- and pro- apoptotic proteins is determinant of cell death/survival
XIAP is (X) with affinity for (Y).
X = caspase inhibitor protein
Y = active caspases
What’s the Smac-DIABLO pathway?
Apoptotic pathway in which Smac/DIABLO protein inhibits apoptotic/caspase inhibitor XIAP
The p53 protein is an example of a(n) (X) that acts by affecting:
X = tumor suppressor
Transcription (regulates expression of various genes)
How does p53 (prevent/induce) apoptosis?
Induces
- Increases transcription of Bax and Noxa
- Activates cytoplasmic Bax to bind mitochondrial membrane
- Increases p21 expression (cell cycle arrest)
Raf, a(n) (X) protein, (prevents/induces) apoptosis by:
X = MAP kinase
Prevents;
Phosphorylates Bad, leading it to dissociate from mitochondrial membrane
One way to prevent apoptosis is (X) of Bad, causing its (increased/decreased) enhancing action on (Y). Name some enzymes that have this function.
X = Phosphorylation
Decreased
Y = Bax and Bcl-XL
Raf and Akt
