Cell Cycle (Control of cell division) Flashcards
Three fundamental processes determining organ and body size
- Cell Growth
- Cell Division
- Cell Survival
Extracellular signal molecules that regulate cell growth, division and survival
Mitogens
Growth factors
Survival factors
secreted proteins, proteins bound to the surface of cells, or components of the extracellular matrix
extracellular signal molecules
stimulate cell division; G1/S-Cdk activity
Mitogens
stimulate cell growth; synthesis of proteins and other macromolecules
growth factors
promote cell survival; suppressing apoptosis
Survival factors
cell proliferation means?
cell growth
Their rate of proliferation depends on the availability of nutrients
unicellular organisms
They divide only when the organism needs more cells
multicellular organisms
anima cell receive stimulatory extracellular signals in the form of _____ to proliferate
mitogens
-first mitogen identified; observation that fibroblasts in a culture dish proliferate when provided with serum not when provided with plasma.
-stimulate many types of cells to divide (fibroblast, smooth muscle cells, neuroglial cells).
Platelet-derived growth factor (PDGF)
acts not only on epidermal cells but also on many other cell types, including both epithelial and nonepithelial cells
epidermal growth factor (EGF)
only induces the proliferation of red blood cell precursors
erythropoietin
inhibitory extracellular signal protein; inhibit proliferation
transforming growth factor-B (TGFB) B for beta
Cdk inhibition in G1 is maintained. by the multiple machanisms discussed, and progression into a new cell cycle is blocked.
absence of a mitogenic signal
specialized nondividing state
G0
neurons and skeletal muscles; cell-cycle control system is completely dismantled
terminally differentiated G0 state
the expression of the genes encoding various Cdks and cyclins is permanently ______ ___, and cell division rarely occurs
turned off
mitogens control the rate of cell division by acting in the __ _____ of the cell cycle
G1 phase
Mitogens interact with cell-surface receptors to trigger?
multiple intracellular signaling pathways
One major pathway acts through the monomeric GTPase Ras, which leads to the activation of a?
mitogen-activated protein kinase (MAP kinase) cascade.
the activation of mitogen-activated protein kinase (MAP kinase) leads to an increase in the production of?
transcription regulatory proteins, including Myc
Myc is thought to promote cell-cycle entry by several mechanisms, one of which is to increase the expression of genes encoding __ ______
G1 cyclins (G1 Cdk)
bind to specific DNA sequences in the promoters of a wide variety of genes that encode proteins required for S-phase entry
E2F proteins
In the absence of mitogenic stimulation, E2F-dependent gene expression is inhibited by an interaction between E2F and members of the ______________ _______ (Rb) family.
retinoblastoma protein
a result of spontaneous chemical reactions in DNA, errors in DNA replication, or exposure to radiation or certain chemicals
DNA damage
cell-cycle control detects DNA damage and arrest the cycle
Start and G2/M transition
DNA damage initiates a signaling pathway by activating one of a pair of related protein kinases called ___ and ___.
ATM and ATR
ATM and ATR associate with the site of damage and phosphorylate various target proteins, including two other protein kinases called ____ and ____.
Chk1 and Chk2
stimulates transcription of gene encoding p21
p53
binds to G1/S-Cdk and S-Cdk complexes and inhibit their activities, thereby helping to block entry into the cell cycle.
p21
undamaged cell, p53 is highly unstable and is present at very ___ _____________
low concentration
acts as ubiquitin ligase that targets p53 for destruction
Mdm2
Chk1 and Chk2 phosphorylates Cdc25 family of _______ __________
protein phosphatases
The DNA damage response can also be activated by problems that arise when a replication fork fails during ___ ___________
DNA replication
___ _____ of DNA damage occurs in the normal life of any cell
low level
accumulation of genetic damage in cells lacking the DNA damage response leads to an increased frequency of ______-_________ _________
cancer-promoting mutations
allows the cancer cell to accumulate mutations more easily
mutations in the p53 gene
defect in ATM; very sensitive to x-rays and suffer from increased rates of cancer
ataxia telangiectasia
Many human cells divide a limited number of times before they stop and undergo a permanent ____ _____ ______.
cell cycle arrest
proliferation slows down and finally halts, and the cells enter a nondividing state from which they never recover
replicative cell senescence
Replicative cell senescence in human fibroblasts seems to be caused by changes in the structure of the _________.
Telomeres
-the repetitive DNA sequences and associated proteins at the ends of chromosomes.
-promotes the formation of protein cap structures that protects the chromosome ends.
Telomeres
constant stimulation of Ras-dependent signaling pathways
mutation in GTPase Ras amino acid
overexpression of Myc stimulate excessive ____ ______ and _____________
cell growth and proliferation
excessive mitogenic stimulation
production of Arf (cc inhibitor protein)
production of Arf (cc inhibitor protein)
inhibits Mdm2
inhibits Mdm2
p53 levels increase
p53 levels increase
cell-cycle arrest or apoptosis
cell growth accompanies ____ _______
cell division
stimulate the accumulation of proteins and other macromolecules
increase rate of synthesis and decrease rate of degradation
activation of a kinase TOR
phosphoinositide 3-kinase (PI 3-kinase)
activates many targets in the cell that stimulate metabolic processes
activation of a kinase TOR
S6K
S6 kinase
translation initiation factor
elF4E
describe a factor that has any of these activities
growth factor
withdraw from the cell cycle and re-enter the cycle when damage
Liver cells
do not produce telomerase, their telomeres become shorter with every cell
division, and their protective protein caps progressively deteriorate
human fibroblasts
the exposed chromosome ends are sensed as DNA damage, which activate
p53-dependent cell-cycle arrest (
have regained the ability to produce telomerase and therefore maintain telomere
function as they proliferate
cancer cells
mitogenic signaling pathways are encoded by genes
that were originally identified as
cancer-promoting genes
