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85 Cards in this Set

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What occurs in G1(gap) phase?
• Cell prepares for DNA replication;
Intensive synthesis of proteins and RNA, including proteins engaged in the regulation of the cell cycle;

This leads to increased cell volume.
The nucleoli are reestablished.
What occurs in s (synthetic) phase?
Synthesis of histones and DNA (replication) by polimerases (α i δ); Alfa + delta
What occurs in G2 phase?
Preparation for mitosis,
more RNA and proteins are synthesized,
energy is stored, tubulin in synthesized,
DNA is analyzed for errors.

there are four copies of each chromosome in the cell (2n4C - 46 chromosomes but 92 chromatids
Cyclin D is synthesized when?
Early G1 phase
Cyclin E is synthesized when?
Late G1 phase
Cyclin D binds to?
CDK4 and CDK6
Cyclin E binds to?
CDK2
cyclinD/CDK4
cyclinD/CDK6
cyclinE/CDK2 complexes do what when?
In G1 phase,
Permits the cell to enter and progress through S phase.
Cyclin A binds to?
CDK2 and CDK1
cyclinA/CDK2
cyclinA/CDK1 complexes do what when?
S phase,
Permits the cell to leave S phase and enter G2 phase and induce the formation of Cyclin B
Cyclin B bind to?
CDK1
Once the cyclins have done its take they enter the?
Ubiqutin-proteasome pathway where they are degraded
Karyokinesis is?
the actual division of the cell nucleus into two daughter nuclei during mitosis.
5 examples that can induce apoptosis?
Acute injury,
accidents,
lack of vascular supply,
destruction of pathogens or immune system,
genetic programming
G2/M checkpoint checks for?
proper cell size, DNA replication is completed
M checkpoint checks for?
proper alignment of chromosomes on mitotic spindle
Completion of M checkpoint leads to?
completion of karyokinesis and triggering of cytokinesis
Restriction point R is where?
Late G1 phase
Restriction point R checks for?
proper cell size
proper external environment
presence of growth factors
Three characteristics of Cyclins?
no enzymatic activity,
regulatory subunit,
cyclical changes in the cyclin protein level
Three characteristics of Cdk (cyclin-dependent kinases)?
activated by cyclins,
catalytic subunit – protein kinase activity,
level of cdk protein is constant,
activity is regulated by cyclins
cyclinB/CDK1 complex is also called?
MPF (Mitosis Promoting Factor, M-phase Promoting Factor)
cyclinB/CDK1 complex do what when?
G2 phase,
allow the cell to leave the G2 phase and enter the M phase
increase of concentration of MPF leads to?
cell enters the prophase,
condensation of chromosomes,
damage of the nuclear envelope,
mitotic spindle formation
decrease of concentration of MPF leads to(in mitosis)?
cell enters the anaphase
decrease of concentration of MPF leads to(in cell cycle)?
segregation of chromosomes,
decondensation of chromosomes,
repair of nuclear envelope,
DNA replication,
duplication of centrosome
Anaphase Promoting Complex(APC) triggers what and how?
Transition from metaphase to anaphase by tagging specific proteins for degradation (ubiquitination)
(Lower MPF levels)
How can MPF start the break down of the nuclear envelope?
phosphorylates serine residues of lamins ->
lamin filaments depolimerize ->
nuclear envelope breaks up into bubbles
Activity of cyclin-Cdk complex is regulated by?
degradation of cyclins.
cyclinD/CDK4
cyclinD/CDK6 Complexes acivates?
Rb protein, which stimulates synthesis of cyclin E (Enter S phase)
cyclins D production is induced by?
Growth factors
Detection of damaged DNA results in phosphorylation of?
p53 protein
p53 protein stimulates the synthesis of?
p21, which is an inhibitor of cyclin-dependent kinases (CDKs)
Major inhibitors of CDKs?
Ink3 family(P15,p16,p18,p19) and
CIP/WAF family(p21, p27, p57)
Cell cycle is arrested in G1/S (due to p53->p21 ) until?
damaged DNA is repaired
The characteristics of tumor cells:
Self-sufficiency in growth signals,
Insensitivity to growth-inhibitory signals,
Evasion of apoptosis,
Limitless replicative potential,
Angiogenesis,
Ability to invade and metastasize,
Defects in DNA repair
The most important tumor suppressor genes associated with cell cycle control?
P53 and Rb proteins
ASC (Adultstemcells) are present in?
most tissues and organs as tissue stem cells - a small portion of all tissue cells
Adultstemcells (ASC) present in?
Found in tissues of adult organisms, multipotent (hematopoetic cells) or unipotent (muscle satellite cells);
Intestinal epithelial cells are completely replaced within?
a few days
The bone is completely replaced within?
10 years
The epidermis is renewed within?
two months.
Mitogens is a?
chemical substance(protein) that encourages a cell to commence cell division, triggering mitosis
mitogens stimulate cell devision by?
relieving intracellular negative controls (ex. RB) that block progress through the cell cycle. This is done by activating 1/S-Cdk complexes
Three major Extracellular groups that control cell division, cell growth and apoptosis:
mitogens, Growth factors and Survival factors
Some signaling proteins may be both mitogens and growth factors - example?
PDGF, they help to maintain the proper cell size during proliferation.
growth factors stimulation leads to what within the cell?
They lead to the accumulation of proteins and other macromolecules by increasing the rate of synthesis and reducing degradation processes(of cyclins)
why is Survival factors used?
to maintain only the cells that are needed, and only where they are needed.
How can Survival factors protect against apoptosis?
They induce Bcl-2, prevent leakage of mitochondrial proteins (Cyt C)
Name 1 anti-apoptotic protein and what do they do?
Bcl-2,
These proteins maintain the integrity of mitochondrial membranes and prevent leakage of mitochondrial proteins(Cytochrome C)
Name 2 pro-apoptotic proteins and what do they do?
Bax and Bak (both from Bcl-2 protein family)
They form channels in the mitochondrial membrane
-> cytochrome c leaks out together with IAP inhibitors
Name 1 Extracellular inhibitory protein:
Myostatin(TGT-beta family) -
inhibits the proliferation of myoblasts that fuse to form skeletal muscle cells
Stages of apoptosis?
Initiation phase, Effector phase, Degradation phase
What are caspases?
intracellular proteases(proteins) that will trigger Apoptosis
stress-induced apoptotic pathway (intrinsic) – can be induced by?
increased concentration of calcium ions in the cell,
oxidative stress,
DNA damage,
degradation of microtubules
Mechanisms of Intrinsic pathway(apoptosis)?
involves the action effectors of the Bcl-2 family (Bax + bak), which induce leakage of mitochondrial proteins and cytochrome c–dependent caspase activation.
Cell differentiation is regulated by?
the activation of genes coding for transcription factors which activate other genes, resulting in expression of receptors for growth differentiation
The INK4 family (p15, p16, p18, p19) acts on?
selective effects on cyclin D/CDK4 and cyclin D/CDK6.
The CIP/WAF family(p21, p27, p57) acts on?
acts on all CDKs
Apoptosome is a ?
complex composed of Apaf-1 protein, cytochrome c and caspase-9.
caspase-9 on the Apoptosome is a initiator capase and do what?
Cleaves Pre-caspase 3 into active caspase 3
IAPs are what and do what?
"Inhibitors of Apoptosis", inhibits caspase
midbody is what?
The midbody structure contains bundles of microtubules derived from the mitotic spindle which compacts during the final stages of cell division.
synaptonemal complex?
protein structure that forms between chromosomes during meiosis and that is thought to mediate chromosome pairing, synapsis, and recombination
chiasmata is what?
the point at which members of a chromosome cross over
progenitors cells are?
like a stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its "target" cell.
what happens during epigenetic modification?
alters the extent to which the DNA is wrapped around the histones, becomes more or less transcribed
stem cell niche is a?
microenvironment where stem cells are found, maintain adult stem cells in a quiescent state
stem cell niche in adults is "activated" when?
after tissue injury, the surrounding micro-environment actively signals to stem cells to either promote self renewal or differentiation to form new tissues.
metaplasia?
Cells change cell type to suite the environment better
quiescence?
cells that are reversible in G0 stage
senescent?
Old cells that will no longer divide yet has active metabolism
phosphatidylserine?
A phospholipid component that is on the inner leaflet, during apoptosis it flips and is on the external side and is recognized by macrophages.
The INK4 family (p15 p16, p18, p19) acts on?,
selective effects on cyclin D/CDK4 and cyclin D/CDK6.
The CIP/WAF family(p21,p27, p57) acts on?,
acts on all CDKs
IAPs are what and do what?
"Inhibitors of Apoptosis", inhibits caspase
What are Kinases?
type of enzyme that transfers phosphate groups from ATP to specific substrates, a process referred to as phosphorylation.
What are Cytochrome c?
is a small heme protein found in inner membrane of the mitochondrion,essential component of the electron transport chain
What are Caspases?
Family of proteases, major effector of apoptosis process
PCNA
(proliferating cell nuclear antigen) – coenzyme of polymerase δ(Delta) is a marker of phase S and is permanently associated with the nucleus
The importance of the restriction point R (G1 phase checkpoint)
• Cell must decide whether to:
- leave the cell cycle temporarily(stateof
quiescense)
- Finally leave the cell cycle(aging),
- Enter the cellcycle,
- differentiate,
- die.
Cdk inhibitory proteins are active during what phase and why?
Cdks are inactive for most of the G1 phase

Delay in the progression of cells into the next phase of the cell cycle - S phase - gives them time for growth stimulated by growth factors leading eventually to the next division.

- The inhibition of G1 phase terminates when G1 cyclins accumulate after stimulation of the cells to divide by growth factors
The molecular mechanisms responsible for the inhibition of the cell cycle at specific checkpoints:
protein inhibitors of Cdks – block the formation or activity of one or more of the cyclin-Cdk complexes;

p53 protein – transcription factor with tumor suppressor properties
Mechanisms of extrinsic pathway(apoptosis)?
+initiated by?
death receptor – initiated apoptotic pathway – is initiated by engagement of plasma membrane death receptors (TNF-R, CD95);

Leads directly (No BCL-2 involvement) to activation of caspases 8 -> caspases 3
cdc25c phosphatase do what
Remove inhibitory phosphorylation from CDK1 -> mitosis