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8. Cell cycle control and cell growth control
BrownMed
56
Art/Design
5th Grade
11/02/2010

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Term
cell replication requires (2)
Definition
duplication of cellular contents, division into two cells
Term
limiting facto in prokaryotes
Definition
nutrient availability
Term
G1
Definition
most variable duration. cell contents double (but DNA doubles in S phase)
Term
G2
Definition
prep for mitosis
Term
M
Definition
mitosis ~ 1hr long
Term
G0
Definition
quiescence from which cells can reenter G1
Term
permanent growth arrest
Definition
terminal diff or senescence
Term
typical human cell cycle time
Definition
24-36 hours
Term
components of cell cycle machinery (3)
Definition
cyclins, cyclin-dependent kinases, cyclin-dependent kinase inhibitors
Term
how are cdk's activated and what do they do
Definition
activated when cyclin binds; cdks phosphorylate other things
Term
cyclin D's cdks and site of action
Definition
4 and 6; G1
Term
E's cdks and site
Definition
2, late G1 and early S
Term
A's cdks and site
Definition
2, S and G2
Term
B's cdks and site
Definition
1, M
Term
t/f the expression of cyclins in the D family is uniform throughout cell types
Definition
false - hepatocytes and B/T cells are different
Term
cyclin protein levels
Definition
are cyclical and therefore regulate cdk activity (cdks have constant protein levels)
Term
what kind of kinases are cdks
Definition
ser/thr; few are PY
Term
CKI
Definition
key regulator of cell cycle progression and other cell processes - apoptosis, differentiation. binds to cyclin/cdk complex, which inhibits cdk activity
Term
2 main classes of CKIs and basic stuff
Definition
INK and KIP. INK is only ever active in G1.
Term
clinically relevant CKIs (2)
Definition
p21 (KIP) - induced in response to DNA damage. p16 (INK) - mutated in many human tumors.
Term
formation of active cyclin/cdk complexes requires (4)
Definition
adequate cyclin levels, cdk presence, CKI at sufficient but low level, ability of CAK or other kinase to phosphorylate the complex while suppressing the relevant phosphatase
Term
CAK
Definition
cdk-activating kinase
Term
cdk activity is regulated by (3)
Definition
cyclin content, cki content, phosphorylation status
Term
cyclin content is regulated at the level of (3)
Definition
transcription, translation, protein degradation
Term
CKI content is regulated at the level of (3)
Definition
transcription and protein degradation only
Term
control of cki cdk and cyclin is downstream from (2)
Definition
growth factor signaling pathways and intrinsic regulatory cell mechanisms
Term
restriction point
Definition
separates g1 phase; 1st = requires continuous mitogenic signals and a high rate of protein synthesis. interruption of this phase leads to quiescence (G0). once the cell passes through restriction point it becomes committed to DNA synthesis and cell division.
Term
Rb
Definition
retinoblastoma protein, regulates partially the restriction point. is a focal point for malignancy in newborns.
Term
before G1 restriction point, Rb
Definition
is hypophosphorylated and bound to transcription factor E2F, which inactivates E2F.
Term
tumor suppressor
Definition
Rb
Term
cell cycle basic pathway
Definition
external signals like growth factors and integrins > MYC, RAS and other genes > cyclin D > active D/cdk4 complex *> Rb phosphorylation > active E2F >>> cell cycle. *: inhibited by p16 and p21, so if either of those is mutated, you probably get cancer.
Term
terminally differentiated cells examples? (2)
Definition
neurons, skeletal muscle cells
Term
cells that proliferate when needed examples (2)
Definition
immune, hepatocytes
Term
how is senescence different from term. diff.
Definition
senescence is due to lack of nutrients, term. is due to need of those cells
Term
overexpression of D and E (3)
Definition
breast and testicular cancer, leukemia
Term
Rb mutational inactivation (3)
Definition
osteosarcomas, small cell lung carcinomas, Rb
Term
cervical cancer - specific protein
Definition
sequestration of Rb by HPV E7 protein
Term
deletion or mutation of CKI genes
Definition
prostate cancer
Term
regulation of cell growth: c-Myc and MTOR.
Definition
c-Myc (proto-oncogene) > when expressed, activates RNA Pol I > synthesizes rRNA > ribosomes synthesized > size is best correlated with ribosome number > cell doubles its size to pass into S phase. MTOR (nutrient-sensing kinase) activates 5'TOP transcription > ribosomal proteins > ribosomes > lots = size > doubled size
Term
permanent quiescence =
Definition
senescence
Term
cancer cells often demonstrate _ of cell size
Definition
dysregulation = they're smaller
Term
pathways to regulate synthesis of _ differ in cancer cells
Definition
ribosomes
Term
how does cancer just keep growing?
Definition
arteries grow with it to provide nutrients, but the middles of tumors often necrose anyway
Term
how do we define growth? (2)
Definition
hypertrophy = cell growth, proliferation = requires cell growth
Term
what causes cells to proliferate and hypertrophy in bone?
Definition
IGF-1
Term
replicative senescence and final height
Definition
there is a limit to the number of times cells in resting zone of bones can divide. timing differs between individuals. once cells in resting zone are no longer proliferating, growth plate closes
Term
is there a hormone that regulates senescence in the resting zone of bones?
Definition
estrogen
Term
what is greater in bigger people: proliferation or hypertrophy? what does a null mutation of IGF system cause?
Definition
proliferation, which depends upon hypertrophy. mutation causes decreased cell number
Term
IGF-I block
Definition
60% proportional mouse
Term
IGF-II block
Definition
60% proportional mouse
Term
IGF-I block and IGF-II block
Definition
30% proportional mouse
Term
IGF-I receptor block
Definition
45% proportional mouse
Term
what kind of diet promotes longer life, and why?
Definition
low protein, low calory. because IGF-I is not as activated. mechanism unknown, but the smaller you are, the longer you live.
Term
15-megabase region on chromosome 15 (IGF1)
Definition
gene region for size determination in dogs
Term
what is present in small dogs but not big dogs
Definition
a single-nucleotide polymorphism haplotype
Term
3 main things that don't happen if people eat less
Definition
cancer, CVD, diabetes
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