cell cycle and cancer Flashcards
eukaryotic cell cycle master controllers are a few protein ___ that contain what 2 subunits
protein kinases
cyclin, catalytic subunit (cyclin-dependent kinase [CDK])
cell cycle phases
G1 (first gap)
S (sythesis)
G2 (second gap)
M (miotic - prophase, metaphase, anaphase, telophase)
Go (resting phase)
what phases count as interphase and how long does it take vs how long does mitosis last
G1,S,G2 (16-24 hrs)
mitosis - 1-2 hr
G1
S
G2
M
G1 - grow, synthesize RNA and proteins for DNA synthesis
S - chromosome replication
G2 - rapid growth and protein synthesis
M - cell division
-Initiates mitosis
-Gradual condensation of chromosomes
-Disintegration and eventual disappearance of the nucleolus
-Beginning of formation of miotic spindle
-Centrosomes (pair of microtubule organizing centers) from which microtubules radiate
-Centrosomes gradually move to take up positions at poles of cell
-Separation of centrosomes
Prophase
-Enters when nuclear membrane breaks up
-Chromosomes disperse within the cell and attach via kinetochores, to microtubules of the mitotic spindle
-Chromosomes begin to move toward a point midway between the spindle poles
-Chromosomes continue to condense throughout this stage
-Microtubules attach to chromosomes
-Chromosome forms 2 kinetochores at centrosome
Pro-metaphase
-Chromosome algin in the metaphase plate
-Chromosome reach maximal condensation
-Chromosomes become arranged at the equatorial plane of the cell
-Chromosome of a divind human cell is most readily analyzed at the metaphase stage of mitosis
Metaphase
-Chromatids separate words opposite poles
-Begins abruptly when the chromosomes separate at the centromere
-Sister chromatids of each chromosome now become independent daughter chromosomes, which move to opposite poles of the cell
Anaphase
-New nuclear envelop forms
-Chromosomes unfold back into chromatin
-Nucleoli reappearance
-Cell continues to elongate
-Chromosomes begin to decondense from their highly contracted state
-Nuclear membrane begins to reform around each of the 2 daughter nuclei and each nucleus gradually resumes its interphase appearance
Telophase
cytokinesis
separation of the 2 daughter cells
cell cycle checkpoint in mitosis
anaphase is blocked if chromatids are not properly assembled on mitotic spindle
R point
decide to continue or go G0
B-CDK1 what phase
M phase
D-CDK4/6 what phase
G1 phase
E-CDK2 what phase
G1 and S phase
A-CDK2 what phase
S phase
A-CDK1 what phase
S and G2 phase
CDK inhibitors suppress the formation of what
tumors (are tumor suppressor proteins)
INK4 proteins (inhibitors of CDk4) affect what
CDK4/6
cip/kip proteins affect what
CDK1/2
members of INK4 proteins
p16INK4A, p15INK4B, p18INK4C, p19INK4D
members of cip/kip proteins
p21CIP1 (or p21Waf1), p27Kip1, p57Kip2
mitogens do what to inhibitors
proliferative (inhibits the inhibtors) (favor cell cycle advance)
antiproliferative do what to inhibitors
activate inhibitors (block cell cycle)
Rb protein initially inhibits what
E2F acitvity
stimulation of G0 cells with mitogens induces expression of what
CDK4, CDK6, D-type cyclins, E2F transcription factor
in the presence of mitogens, what does cyclin D-CDK4/6 do
phosphorylates Rb protein
E2F does what
stimulates gene transcription
phosphorylated or unphosphorylated Rb is inhibiting E2F
phosphorylated Rb is not inhibiting E2F
Rb is a what type of protein
tumor supressing protein
important hallmark of cancer
evading growth supressors
what is mutated in several cancers
p53
what are the two prototypical tumor suppressor genes
p53 and Rb
p21Cip1 is activated by what
p53
what is p53 trying to do, and so what happens if its mutated
halt cell cycle if theres damage
if its mutated, proliferation keeps going w the damage
ATM and ATR are what and do what
protein kinases
sense DNA damage and trigger cell cycle arrest
how can cancer cells spread
through blood and lymphatic systems
what causes sustaining proliferative signaling
growth factors
autocrine proliferative stimulation
Rb
tumor supressor protein
p53
tumor supressor protein
TGF-B
antiproliferative protein
NF2/Merlin
tumor suppressor protein, orchestrates contact inhibition
loss of normal p53 important why
p53 is a critical damage sensor (usually apoptosis would occur)
extrinsic apoptosis pathway
bind to cell surface receptors-death receptors (DRs)
intrinsic apoptosis pathway
involves damage to nuclear DNA as well as mitochondria
triggered by agents such as ROS
necrosis
release proinflammatory signals into the surrounding tissue environment, and immune inflammatory cells can be tumor promoting due to fostering angiogenesis, cancer cell proliferation and invasiveness
necrotic cells can release
