Exam 3 pt 3 Flashcards
RhoA
Monomeric GTPase which controls the assembly and contraction of the contractile ring
RhoA is turned on by
RhoGef, localized in the cell cortex at the future site of cell division
RhoA - GTP activates
formins which nucleat the growth of straight unbranched actin that can form parallel bundles
Phosphorylation of the _ by Rho-GTP kinases triggers
myosin regulatory light chain, triggers activation of myoson 2 whic assembles the contractile ring and contracts it
midbody
A narrow structure connecting daughter cells near the end of cytokinesis, it contains tightly packed microtubules derived from the antiparallel interpolar microtubules of the spindle midzone surrounded by a dense matrix material
_ initiates cytokinesis
dephosphorylation of Cdk substrates (due to APC/C mediated destruction of cyclins)
location of the cleavage in cytokinesis is determined by
mitotic spindle
astral microtubles
carry signal to the cell cortex which specify the site of furrow formation
spindle midzome
generates signals that specify the site of cleavage furrow formation
astral microtubles
promote the relaxation of actin myosin bundles except at site encircling the midzone of the spindle
for asymmetric division to occur
the spindle poles must be located assymetrically in the mother
syncytium
A large mass of cytoplasm, surrounded by a plasma membrane and containing multiple nuclei. It is formed when nuclear division occur in the absence of cytoplasmic division
cellularization
A coordinated round of cytokinesis during which membranes form around each nucleus of a syncytium, resulting in a multicellular structure
inactivation of _ occurs in late mitosis
Cdks
G1 phase in rapidly dividing cells
- APC/C activated by Cdc20
- activation depend on M-Cdk
- as M-cyclin levels fall, Cdc20-APC/C activity decreases
- Cdks reactivated immediately after mitosis
embryonic cells with no G1 phase
slower diving cells G1 phase
- APC/C activation prolonged by Cdh2
- activation inhibited by M-Cdk
- as M-cyclin levels fall, Cdh1-APC/C takes over for Cdc20-APC/C
- Cdks remain inactive through late mitosis until early G1
cells with G1 phase
Cdk activity low after mitosis due to
CKIs
p21
A CKI (Cdk inhibitor) whose transcription is stimulated by the gene regulatory protein p53. It binds to and inactivates G1/S-Cdk and S-Cdk, causing cells to arrest in G1.
p53
Gene regulatory protein activated by DNA damage, it functions to block progression through the cell cycle. Mutated forms of this protein are found in half of all human cancers.
Mitogens
Class of extracellular signal molecules which promote cell proliferation
Growth factors
Class of extracellular signal molecules which promote cell growth by triggering increased synthesis and decreased degradation of cellular molecules
Survival factors
Class of extracellular signal molecules which suppress apoptosis
platelet-derived growth factor (PDGF)
A mitogen which stimulates the proliferation (as well as growth, survival, differentiation and migration) of a large number of cell types; it is released from blood clots to help stimulate cell proliferation during wound healing
epidermal growth factor
stimulates proliferation on a wide variety of cell types
erythropoietin (EPO)
stimulates proliferation of RBC precursors
transforming growth factor beta
inhibits cell division by blocking progression through cell cycle or promoting apoptosis
G0
State of withdrawal from the cell cycle, it may be transient or permanent (as with termially differentiated cells such as neurons)
Myc
Gene regulatory protein, its production increased in response to the MAP kinase cascade, which promotes cell-cycle entry by several mechanisms, including increased expression of genes encoding G1 cyclin
Retinoblastoma protein (Rb) family
Protein family which, in their unphosphorylated form, bind to and inhibit E2F gene regulatory factors, thus blocking entry into S-phase. This protein family was originally identified in children with an inherited form of eye cancer.
_ inhibits Rb, causing Rb to
G1-Cdk inhibits Rb, causing Rb to release and activate a group of gene regulator factors called E2F proteins
DNA damage response with p53
p53 = cell cycle arrest
* p53 usuallt bound and ub by Mdm2 and destroyed in proteasomes
* phosphorylation of p52 blocks Mdm2 binding, buildup of p53
* p53 binds p21 regulator region, stimulate expression of p21
* p21 inactivate G1/S-Cdk, arresting cells in G1
DNA damage response with Chk1/Chk2
- M-Cdk initional inactive due to presence of inhibitory phosphates
- Cdc25 remove inhibitory phosphates
- when DNA damage, Chk1 and Chk2 phospho and inhibt Cdc25, blocking progression into mitosis
replicative cell sencence
Phenomenon in which cell proliferation halts after a finite number of cell divisions, apparently due to loss of telomeres
Arf
In response to abnormal mitogenic stimulation, this protein associates with Mdm2, preventing its binding and ubiquitylation p53, resulting in p53 accumulation and the triggering of p53-driven cell cycle arrest or apoptosis
TOR
A protein kinase activated by the PI 3-kinase cell growth pathway, it is an important component of growth regulatory pathways in all eukaryotes. It activates many targets that stimulate metabolic processes, including increased protein synthesis
for a cell to maintain its size,
it must double in size before dividing
nerve growth factor
secreted by neuron to make neuron larger
A large multiprotein complex called ___________________ binds to replication origins throughout the cell cycle.
origin replication complex
The formation of prereplicative complexes is referred to as _____________________ since initiation of DNA synthesis may only occur at origins containing a pre-RC.
licencing of replication
When cells undergo nuclear division without cytoplasmic division a ___________________ is formed.
syncytium
Extracellular signal molecule that stimulates cell proliferation.
mitogen
Stage of mitosis when the mitotic spindle disassembles.
telophase
The assembly and contraction of the contractile ring is controlled by
the small GTPase RhoA.
APC/C is a member of the
ubiquitin ligase family of enzymes.
The major components of the contractile ring are
actin filaments and myosin II filaments.
The continued activation of APC/C into G1 is due to the binding of ___________________, a process which only occurs in the absence of M-Cdk activity.
chd1
The_ triggers both anaphase and cytokinesis.
inactivation of Cdks by the action of APC/C
DNA replication begins at sites scattered at numerous locations on each chromosome called
origins of replication.
For full activation of a cyclin-Cdk complex, an enzyme called _______________ must phosphorylate an amino acid near the Cdk active site.
Cdk-activating kinase
For full activation of a cyclin-Cdk complex, an enzyme called _______________ must phosphorylate an amino acid near the Cdk active site.
Cdk-activating kinase
Complex of proteins that holds sister chromatids together until they segregate at anaphase.
cohesion
the duplication of centrosomes occurs in
S phase
At least half of all human cancers have mutations in .
p53
The _ ends of kinetochore microtubules are attached to the _ by the _
plus, kinetochores of chromatids, Ndc80 complex
Many human cells divide a finite number of times before going into permanent arrest, a phenomenon called _ which appears to be caused by the loss of telomeres.
Replicative cell senescence
Many human cells divide a finite number of times before going into permanent arrest, a phenomenon called _ which appears to be caused by the loss of telomeres.
Replicative cell senescence
Cell cycle checkpoint at which APC/C is activated.
Metaphase-to-anaphase transition
The assembly of pre-RCs is inhibited by _ and stimulated _
Cdk activity (S phase to early mitosis), by APC/C activity (late mitosis to early G1)
Nuclear envelope breakdown occurs during
prometaphase
cell death is important
in both developing and adult tissues
apoptosis
- cell remains intact
- rapidly removed by phagocytes
- no inflammation
- more common
- cell shrinkage
- cytoskeleton collapse
- mediated by proteolytic enzymes called caspases
necrosis
- cell burst and spill content
- inflamation
necrosis
- cell swell and burst and spill content
- inflamation
- triggered by acute insult (e.g. trauma or ischemia)
_ make apoptotic cells recognizable to
macrophages
caspases
- mediate apoptosis
- proteases specialized
- cys in active site, target Asp
procaspases
inactive soluable form of initiator caspases, need to be cleaved to become active caspases
apoptotic signals trigger
binding of caspases to proteins causing dimerization and acivation
* each caspase cleaves the protease domain of its dimer partner
* cleaved protease domains rearrange into a large and small subunit, active complex
executioner caspases usually exist as
inactive dimers
executioner caspases are activated when
cleaved by intiator caspases
amplifying proteolytic cascade
Self-amplifying and irreversible series of events which lead to cleavage of target proteins and programmed cell death
- happens because one initiator caspase can activate many executioner caspases
executioner capases cleave
many specific target proteins leading to controlled cell death
extinsic pathway of apoptosis activation
- triggered by binding of ligands from TNF family of signal proteins to death receptors of the TNF receptor family
- intercellular death domain recruits FADD
- FADD death effector domain binds to intiator caspase to form a death inducing signaling complex (DISC)
- initiator caspases (procaspases) cleave one another to activate and trigger pathway
FLIP inhibits
DISC by binding in so inhibits extrinsic pathway of apoptosis
intrinsic pathway of apoptosis is a response to
injury, DNA damage, ROS, mitochondrial problems, etc
intrinsic pathway of apoptosis
- internal stimuli and Bcl2 Bek and Bax release cytochrome C from IM space of mitochondria
- cyt c binds Apaf1 and form apoptosome
- each Apaf1 contains CARD which each CARD domain binds initiator caspase 9, activation of CARD domain
anti apoptotic Bcl2 protein
- contain all four BH domains
- Bcl2 and BclX
- Proteins which inhibit apoptosis by binding to effector Bcl2 proteins and preventing their oligomerization within the outer mitochondrial membrane
pro apoptotic Bcl2 proteins
- contain BH1, 2, 3 domains (Bax, Bak) or
- only contain BH3 domain (Bad, Bid)
Bek is located in _ and Bax in _ and both
outer MM, cytosol and both trigger release of cyt C
BH3 only proteins
Pro-apoptotic Bcl2 proteins which bind to and inactivating anti-apoptotic Bcl2, thus allowing the oligomerization of effector Bcl2 proteins within the outer mitochondrial membrane
* promote apoptosis
Bid
- links extrinsic and intrinsic pathways
- extrincsic pathway active then capse 8 cleaves and activates Bid
- Bid then inhibits anti apoptotic Bcl2 proteins and triggers intrinsic pathway
Inhibitors of apoptosis (IAPs)
Proteins which bind to and inhibit (or ubiquitylate) active caspases; they set an inhibitory threshold to prevent the accidental triggering of apoptosis due to spontaneous activation of initiator caspases
_ must be inactivated for apoptosis to occur
IAPs
A large ring complex composed of cytochrome c-bound Apaf1, it recruits and activates initiator caspase-9.
apoptosome
An amplifying proteolytic cascade triggered in response to cell injury, DNA damage, lack of O2, lack of extracellular survival factors or presence of intracellular developmental signals.
intrinsic pathway
Proteases which cleave thousands of specific targets resulting in controlled cell death.
executioner caspases
An amplifying proteolytic cascade triggered in response to the binding of extracellular signal molecules to death receptors.
extrinsic pathway
This domain is missing from decoy receptors, making them incapable of initiating a proteolytic caspase cascade.
death domain
decoy receptors
Cell surface receptors which bind death ligands but lack the cytosolic death domains required to trigger the extrinsic pathway of apoptosis
Abnormal regulation of apoptotic programs often occurs in
cancer cells.
Abnormal regulation of apoptotic programs often occurs in
cancer cells.
Proteins which bind to and inhibit (or ubiquitylate) active caspases; they set an inhibitory threshold to prevent the accidental triggering of apoptosis due to spontaneous activation of initiator caspases.
IAPs
Domain found on both adaptor proteins and initiator caspases; it promotes their association within death-inducing signaling complexes (DISCs)
death effector domain
Homotrimeric transmembrane proteins which are members of the tumor necrosis factor receptor family.
death receptors
Proteolytic enzymes which are the intracellular mediators of apoptosis.
caspases
A type of programmed cell death which causes cells to swell and burst, spilling their contents into the extracellular matrix and potentially triggering immune and inflammatory responses.
necrosis
Decoy receptors…
inhibit extrinsic apoptosis by competing with death receptors for ligand.
Death-inducing signaling complexes (DISC) are formed during the _ pathway of apoptosis.
extrinsic
Domain found on Apaf1 adaptor proteins and initiator caspase-9, it mediates the recruitment of the initiator caspase into an apoptosome.
CARD
An intracellular blocker of apoptosis, it resembles an initiator caspase but lacks a proteolytic domain.
FLIP
Complex in which initiator caspases are brought into close proximity and activated in the extrinsic pathway of apoptosis.
DISC
The amplifying proteolytic caspase cascade begins with the self-activation of _ caspases.
initiator
cancer arises from mutations that cause a cell
to become asocial and behave selfishly
cancer cells two properties
- abnomal proliferation
- invasiveness
neoplasm
A term meaning ‘new growth’, it describes a tumor arising from the growth and proliferation of a cell in defiance of normal controls
benign tumor
A tumor which is self-limiting in growth and non-invasive; it can be cured by removing or destroying the mass
malignant tumor
A tumor whose cells have acquired the ability to invade other tissues, an essential characteristic of cancer
- form metastases
metastases
A secondary tumor that arose from a malignant primary tumor
carcinoma
Derived from epithelial cells, it is the most common type of human cancer
adenocarcinoma
Cancer derived from glandular tissue
sarcoma
Cancer derived from connective tissue or muscle cells
leukemias
Blood cancer derived from white blood cells and their precursors
lymphoma
Cancer derived from lymphocytes and found mainly within lymphoid organs
tumors develop
years before detection
primary tumors
- located at original site where a mutated cell was formed
- arise form proliferation ofo a single abnormal cell
as cells of a primary tumor proliferate,
more mutations accumulate
for a single cell to give rise to a tumor, its aberration must be
inheritable
* mutagenic changes to DNA sequence (caused by carcinogens)
* epigenetic changes
* inheritaed genetic effects (ex. impaired gene repair)
if a single mutation could cause cancer
we would all be yeeted
tumor progression
Process in which a mild disorder of cell behavior evolves gradually into a full-blown cancer
chronic myelogenus leukemia (CML)
Chronic overproduction of white blood cells due to the Philadelphia chromosome translocation
clonal evolution
repeated rounds of mutation, proliferation and natural selection
* as the number of tumor cells increase, so does the chance that at least one cell will undergo a change that favors it
genetic instability results from
mutations that interfere with replication and genome maintainance, therby increasing the mutation rate
cancer cells transformed phenotype
- abnormal cell shape
- abnormal cell motility
- abnomral response to growth factors
