life and death of cell

Question 1

Mitotic cell division and regulation
of the cell cycle:
- its essential for — and —-
- its highly — and —
- De-regulation results in —-

Answer 1

normal growth and development
controlled and regulated
disease pathogenesis e.g:
Cancer

Question 2

cell respond to — and — signals and in response to these the cell choose between :
-Cells signals feed into a network of —- interactions complex situation

Answer 2

internal and external
between stasis, mitosis, apoptosis and sometimes differentiation
partially redundant

Question 3

-External signalling molecules can
bind to — on the cell surface
- Intracellular signalling
pathways will the trigger
activation of —- pathways — the cell

Answer 3

receptors
pro-proliferative
inside

Question 4

Extracellular signals regulating cell
proliferation/cell death:
1. —–: stimulate cell division by relieving intracellular negative controls that block cell cycle progress.

2. GROWTH FACTORS – stimulate cell— (increased cell — ) by
   promoting synthesis of —- and by inhibiting their —- .
3. SURVIVAL FACTORS – promote cell— by suppressing —-
   (programmed cell death)

Answer 4

mitogen
growth
mass
proteins and macromolecules
degradation
survivals
apoptosis

Question 5

Mechanisms regulating the cell cycle:
The standard cell cycle control system is regulated by brakes that
stop the cycle at specific —-

Answer 5

checkpoint

Question 6

Formation of Cyclin-Cyclin dependent kinase (CDK) complexes regulate transition through cell cycle:
1. —– helps promote passage
through the —- point in —
2. —- bind — at the end of —-
and commit the cell to DNA — .
3. —- bind —- during —- and
are required for the initiation of DNA— .
4. —- promote the events of —-.

Answer 6

g1 cyclins
restriction
late g1
G1/S-cyclins
cdks
g1
dna replication
s cyclins
cdks
s phase
dna replication
m cyclins
mitosis

Question 7

• Cyclins + Cyclin dependent kinases (CDK) –> —- —> —-
• CDK catalytic subunit – activity requires —- binding—- = —-
• —- are regulatory subunits which increase and decrease during —– . it acts as a —- for CDL enzyme switching on —- and also its —- at certain point in cell cycle

Answer 7

cyclin dependent kinase complex [CDKC]
kinase activity
substrate
cyclin
= substate
cyclin
cell cycle
substrate
kinase activity
degraded

Question 8

Concentrations of cyclin proteins change throughout the
cell cycle:

Answer 8

check slide 11 so important

Question 9

-E.g. mid-G1 Cyclin/CDK checkpoint:
- Binding of cyclinD —> inactivates —– —> cell cycle —
- In a non-proliferating cell, —
inhibits the formation of an active
Cdk4/cyclin D1 complex.
—- inhibits entry
into the cell-division cycle when
it is unphosphorylated.
- Inactivation of Rb aka —- encourages —- .
Over-activity of (proto-
oncogene) — or — encourages unregulated

Answer 9

Retinoblastoma tumour suppressor protein (Rb)
progresses
p16
Active Rb protein
tumour suppressor
cell division
cdk4 or cyclins d1
cell division

Question 10

Loss of cell cycle regulation in mantle cell lymphoma:
-Expression of cyclin D1 is placed under the control of the —-
- As a result of —- the upregulation of cyclin D1 is —
- Cyclin D1 bound to — activates the
—–, releasing it from — regulation by the —-
- —- drives the cell cycle through the G1-Sphase of the cell cycle

Answer 10

IgH promoter.
chromosomal translocation
induced
CDK4
transcription factor E2F
negative
tumor suppressor Rb.
E2F

Question 11

—– mechanisms can regulate the cellular decision to live or die
p53 ‘Guardian of the genome’ functions include:
1- —-
2- activated by —
3- stops —-
4- p53 mutations are prevalent in many —-

Answer 11

checkpoint
transcription factor
dna damage
cell replicating (G1-S DNA damage check point)
cancers ( ~50% cancers have
p53 mutation)

Question 12

• —- as key regulator of cell proliferation
• —– launch a cascade of signalling events, culminating in the —- and activation of —
• —- is a tumour suppressor that is induced in response to DNA damage.
• Cell cycle arrest leads to — activation, induction of — , inhibition of —- & suppression of — activity.

Answer 12

p53
dna damage sensor
phosphorylation
p53
p53
p53
p21
Rb phosphorylation
E2F

Question 13

• p53 protein is induced in response to —-
• p53 induces —
• p21 inhibits —- of —– and – won’t be phosphorylated and remaining bound to —- this will cause the — genes to not be turned on
• If DNA damage is repaired, — levels drop, —- decreases, cyclin-cdk can
  then phosphorylate — to release — this will lead to —- being turned on and —- proceeds
  -If DNA damage is not repaired, p53 remains — and cell undergoes —-
• p53 is frequently —- in tumours; Tumour cells lacking p53 may
  replicate —- and do not — which leads to —- of further mutations

Answer 13

dna damage
p21
kinase activity
cyclin-cdk complex
Rb
E2F
s phase
p53
p21
Rb
E2F
s phase genes
cell proliferation
remains high
programmed cell death
mutated
damaged dna
don’t die
accumulation

Question 14

— and — controls form at least part of the G1-S cell cycle checkpoint.
—- regulates programmed cell death aka apoptosis

Answer 14

RB and p53
p53

Question 15

A form of cell death in which a
programmed sequence of events
leads to the elimination of cells
without releasing harmful
substances into the surrounding
area is known as —-
—— occurs when a cell is
damaged by an external force, such
as poison, injury, lack of blood
supply etc

Answer 15

apoptosis
necrosis

Question 16

apoptosis is essential to the process of —- and —- as its also a vital mechanism for protecting organisms from —- as —–

Answer 16

normal growth and development
damaged cells
viral infection and cancer

Question 17

• —– signals
  activate cell membranous DEATH
  RECEPTORS
• —- signals trigger release
  of Cytochome c from the
  mitochondion
• Both pathways converge with
  activation of caspases 3, 6 &
  7 leading to —

Answer 17

external
internal
apoptosis

Question 18

regulation of apoptosis:
1- —- singles which is initiated by signals from —- cells
- most cells require signals to stay alive aka — factors as survival and growth factors.
- the absence of — factors causes cells to activate apoptosis
- sometimes cells receive signals to commit suicide from other cells; particularly important in—-

Answer 18

Extrinsic Signals
neighbouring cells
trophic factors
trophic factors
developmental process

Question 19

At about 16 weeks of gestation, apoptosis takes place and an enzyme dissolves the tissue between the fingers and toes which is a normal — apoptotic processes.
- In some foetuses, this process does not occur completely resulting in—-

Answer 19

extrinsic
syndactyly

Question 20

regulating apoptosis:
2- —– cell senses damage and initiates its own death
example:
If DNA damage exceeds the repair
capabilities of the cell —> integrity of DNA is impaired

Answer 20

Intrinsic Signals

Question 21

1- Extrinsic pathway of cell death:
- initiated by formation of —-
- leads to activation of initiator —-
2- Intrinsic pathway of cell death:
- mediated by changes in —-
- regulated by —– family members
- associated with activated of imitator —-

Answer 21

• death-inducing cell surface
  receptor signalling complex (DISC)
• caspase 8
• mitochondrial function
• anti-apoptotic Bcl2 family members
• caspase 9

Question 22

• The extrinsic signalling pathway leading to apoptosis involves —– which are members of the tumour
  necrosis factor (TNF) receptor gene superfamily.
• The most well characterized ligands of these receptors to date are:
• The signal transduction of the extrinsic pathway involves activation of initiator —-
• Activated downstream —- affect several cellular functions as
  part of a process that results in —

Answer 22

transmembrane death receptors
FasL, TNF-alpha, Apo3L, & Apo2L
initiator cascade 8
caspases 3,6& 7
cell death

Question 23

external signal regulating apoptosis:
FasL, or soluble eg. TNFa (tumour necrosis factor), TRAIL are all examples of —-
the activation of these receptors lead to:
1- — binding
2- —- of receptors
3- activation of initiator —
4- activated other — ultimately leading to —

Answer 23

death receptors membrane bound
ligad
trimersation
pro-caspase 8
caspase
apoptosis

Question 24

• The intrinsic signalling pathway for programmed cell death involves —– inducing activities in —- that initiates apoptosis
• Stimuli for the intrinsic pathway include: ——
• —- antagonises anti-apoptotic effect of Bcl-2. this results in —— and release of —- into —-
• Pro-apoptotic proteins activate —-
• cascades induce — which is a hallmark of apoptosis

Answer 24

non-receptor–mediated intracellular signals
mitochondria
viral infections, damage to the cell by
toxins, free radicals, radiation.
Cytoplasmic p53
mitochondrial outer-membrane
permeabilization
cytochrome c
cytosole
initiator caspase 9
dna fragmentation

Question 25

internal signals regulating apoptosis ( continued):
- —– responds to cell damage and induces mitochondrial outer-membrane permeabilization (MOMP)
- this leads to —- leakage from — into —-
- cytc c binds to —-
- cyt c-Apaf1 complex binds to —- and activated it
- —- is formed
- Apoptosome (Cyt c, ATP, Apaf1,caspase 9) activates other — ultimately leading to —-

Answer 25

• cytoplasmic p53
• cyt c
• mitochondria
  -cytoplasm
• APAF1 aka (apoptotic protease activating factor)
• initiator caspase 9
• apoptosome
• caspases
• apoptosis

Question 26

Summary of caspase activation:
- Initiator caspases (eg Caspase 8 and 9) cleaved in response to —- from other classes of — and then activate the —–
- the activation of caspases results in :
dna fragmentation by — and loss of —- and — breakdown , cell fragmentation into —- and then these bodies get phagocytosed by —–

Answer 26

activation signals
classes of proteins
executioner (effector) caspases.
endonuclease
cell shape
organelle
apoptotic bodies
macrophages

Question 27

-loss of p53 causes unregulated —-
- activated p53 can induce — or —- which is dependent on nature of —-

Answer 27

cell proliferation
cell cycle arrest or apoptosis
stress

Question 28

the inactivation of apoptotic pathway facilitate cancer cell —:
1- the override of — pathway as —-
- dna won’t be — and —- accumulation and the cell doesnt undergo —-
another example is the —- of anti-apoptotic proteins
- the — of BCL2 in numerous forms of leukaemia
2- doesnt respond to — signals:
as —- which bind death signals but don’t transduce signals .
- Fas decoy receptor (DcR3) overexpressed in —
and — tumours – resistant to —

Answer 28

survival
intrinsic
p53 mutation ( p53 mutated in >50% of all human cancers)
repaired
mutagenic lesions
apoptosis
upregulatin
over expression
extrinsic
decoy receptors
lungs and Colon
FasL

Question 29

summary:
- External and internal signals impact cell —
- Cyclin/Cdk complexes play important roles in regulating —-
- P53 responds to — by halting — progression or inducing —-
- Apoptosis can be initiated by —-
- Apoptosis is often— in cancer cells.

Answer 29

cell behavior
cell cycle checkpoint
dna damage
cell cycle progression
controlled cell death aka apoptosis
intrinsic anf extrnsic
switched off