W1D1 - 510 - Cell Bio - Cell Cycle Contol - What Happens When Things Go Wrong?

Front 1

When speaking of cell division, unicellular organisms are restrained only by availability of nutrients, how are multicellular organism are restrained by what?

Back 1

multicellular organisms must restrict division of individual cell for survival of the whole - even in the presence of high nutrients! - why? because it will lead to a competition if don't

Front 2

T/F if something goes wrong with the cell-cycle the cell should die.

Back 2

true, but how?

Front 3

How does a cell die if something goes wrong during the cell cycle?

Back 3

by NECROSIS, or APOPTOSIS

Front 4

___________ is a pathological response to cellular injury. ____________ is a physiological response to specific suicide signals.

Back 4

Necrosis is a pathological response to cellular injury.
Apoptosis is a physiological response to specific suicide signals.

Front 5

Is it necrosis vs. apoptosis that is a passive response, without effort.

Back 5

necrosis

Front 6

Does Necrosis or Apoptosis affect many cells?

Back 6

necrosis, apoptosis affects INDIVIDUAL cells

Front 7

__________ does not require energy from the dying cell.

Back 7

necrosis

Front 8

_________ is an energy-dependent cascade of biochemical and morphological changes within the cell that result in its death and elimination

Back 8

apoptosis

Front 9

Necrosis Vs. Apoptosis:
- chromatin clumps
- chromatin condenses and migrates to nuclear membrane

Back 9

Necrosis - chromatin clumps
Apoptosis: chromatin condenses and migrates to nuclear membrane

Front 10

Does cell death by apoptosis have inflammation?

Back 10

no, LACK of inflammation

Front 11

Necrosis vs Apoptosis - the general inflammatory response is triggered.

Back 11

necrosis

Front 12

Which type of cell death has these features?
- Chromatin condenses and migrate to nuclear membrane
- internucleosomal cleavage leads to laddering of DNA at the nucleosomal repeat length.
- Cell contents are packaged in membrane bounded bodies to be engulfed by neighbors
- Epitopes appear on plasma membrane marking cell as a phagocytic target.

Back 12

apoptosis

Front 13

Does apoptosis or necrosis result in the cytoplasm hrinking without membrane rupture?

Back 13

apoptosis -
necrosis: plasma membrane lyses and cell contents spill out

Front 14

Which type of cell death (necrosis/apoptosis) includes budding off of the cell and then phagocytosis by neighboring cells?

Back 14

apoptosis

Front 15

When does apoptosis occur?

Back 15

In embryonic and fetal development:
- Tissue development programs which control sculpting of embryonic form
- Developmental organization of the nervous system
- Elimination of self - reacting components of the immune system
(Kills 99% of T cells via apoptosis)

Front 16

In nervous system development during embryological development how are the nerve cells retained - what is necessary? Do ALL the cells live?

Back 16

There are nerve cells that have axons extending to target cells and the target cells produce a survival factor so that a 'connection' may be made (if it should be made)
- There is competition and survival that creates single tracts while the others that didn't get the survival factors will die via apoptosis

Front 17

T/F Cell death matches number of nerve cells to number of target cells.

Back 17

True - programmed cell death is pat of development and NATURAL

Front 18

When does apoptosis in an adult occur?

Back 18

on the stimulation of T-lymphocytes

IN RESPONSE TO DNA DAMAGE OR ABNORMALITY
eg; by radiation or viral infection or transformation

in certain organs and tissues, on withdrawal of supporting hormones.

Front 19

T/F the caspase cascade is highly conserved among species

Back 19

true

Front 20

There is only ONE cell NOT programmed to undergo apoptosis...that cell is?

Back 20

sperm in males
egg in females
all other cell are destined to die

Front 21

What exactly do CASPASES do?

Back 21

they are the enzymes that digest cells
- ultimately involved in destruction of DNA - it digests it!

Front 22

T/F death is preferable to life if there is error

Back 22

true

Front 23

P53 is a __________-- _______ which monitors the state of DNA, because it targets RNA pol II.

Back 23

transcription factor

Front 24

What does p53 inhibit?

Back 24

cell cycle progression IF there is damage

Front 25

Following DNA damage (by radiation), p53 levels ______ (rise/fall), and proliferating cells arrest in ___ (G?)

Back 25

RISE, G1

Front 26

What transcription factor stops the cell cycle and allows time for DNA repair prior to the next round of replication.

Back 26

p53

Front 27

What is p53 cell cycle arrest mediated by? (stimulation of what? hint: cyclin kinase INhibitor - was the regu. for G1->S phase and now it can't occur)

Back 27

p21 (very low level present in normal cell)

Front 28

What is constantly being made and constantly be destroyed in the cell/

Back 28

p53

Front 29

DNA damage is sensed by 'checkpoints' in a cell's cycle and causes proteins such as ATM, CHK1, and CHK to PHOSPHORYLATE _______ (different site than MDM2), prevent mdm2 to bind to it and increases number of ____ = inhibits cell cycle so can repair DNA(via p53 binding to the p21 gene = production of p21 (Cdk inhibitor protein that binds to active G1/S-Cdk and puts it into an inactive form)?

Back 29

p53, p53

Front 30

What does Mdm2 do?

Back 30

(normally a heterodimer) phosphorylates and targets for ubiquination of p53 in proteasomes

Front 31

p53 arrests cell in the G1 stage of the cell cycle if there is damage to the DNA; this arrest is to allow repair. If repair doesn't occur, the cell undergoes ______.

Back 31

apoptosis

Front 32

DNA Damage -> Damage response -> either repair or activation of p53 -> TWO things activated
1. Arrest via p21 cyclin kinase inhib
2. Caspase-9
What is the purpose of activating caspase?

Back 32

Caspase kills the cell - thus, it is there in case the repair doesn't occur and lead to apoptosis.
So, p52 also expresses genes that try to kill...
activate them both and start a "race"

Front 33

T/F The functional expression of the gene p53 increases the sensitivity of the expressing cells to activation of programmed death induced by a wide variety of damaging agents

Back 33

True

Front 34

Would genetic alteration of p53 that results in loss of function prevent the cell's ability to undergo apoptosis?

Back 34

yes.

Front 35

Mutation of _____ is associated with many (1/2) of human cancer.

Back 35

p53

Front 36

Such a universally resistant genotype would provide a great selective advantage to any cell so affected ..what does this mean in relation to p53?

Back 36

having the gene = automatic selective advantage
eg: mice with BOTH alleles of p53 knocked out develop multiple malignancies

Front 37

Thus, what would occur if you didn't have p53 to arrest the cell cycle after irradiation?

Back 37

the cell would go through cell division with damaged chromosomes and then end up in one of two options.
1. massive mitotic failure and cell death - TUMOR REGRESSES
2. CANCER; continued mutation, selection, and tumor evolution

Front 38

p53 gene was originally discovered 1979 by Arnold Levine, David Lane, and William Old

Since then, mutant forms of p53 have cropped up in so many tumors and aroused so much interest that Science hailed the p53 protein as the "______________" in 1993

Back 38

Molecule of the Year

Front 39

T/F Perhaps 'death' is the default for many cell types.

Back 39

true

Front 40

The way the cell cycle is controlled, _________________ signals are required for cellular division. (pos or neg)

Back 40

POSITIVE

Front 41

What is Bcl-2? (it's been shown to prevent apoptotic death...how?)

Back 41

"THE CLOCK" that is timing the race activated by p53
- provides the time to repiar the damage
- once Bcl-2 is destroyed it is not inhibiting production of Caspase-9

(basically is inhibitor of the activation of Caspase 9 by p53 - holds off long enough to see if damage to repair will occur)

Front 42

T/F Apoptosis is the 'default' pathway.

Back 42

true

Front 43

When day dreaming about genetic mutation....keep in mind that:

Back 43

Some mutation might result in

- a protein being expressed in the wrong tissue
- genes turned on, or off permanently
- cause the protein to be truncated, or prevent 'folding' of a protein
- prevent the protein from being post-translationally modified (glycosylated)
- prevent a protein from normal protein-protein interactions
(in enzymes) might prevent the processing of other proteins

*some mutations are MUCH worse! What if the mutation affected a cell cycle checkpoint protein???