Smith - Cellular Homeostasis Flashcards
In unicellular organisms:
primary limitation on proliferation is availability of _______ and _______
natural selection favors the cells that ______ more
more division = more mutations = faster ______
when a cell can no longer divide the organism _____
nutrients and energy
divide
evolution
dies
In multicellular organisms:
vast majority of cells are ____ dividing, regardless of availability of nutrients (stop dividing when they bump against one another
______ controls on different cell types
more divisons = more mutations = more _______
when a cell can no longer divide the organism must ___ ______
____ ____ is controlled
not different problems be replaces cell death
In the cell cycle, the cell first ______ its contents, then ______ into ____ _____ ______
duplicate
divides
two daughter cells
The division part of the cell cycle is called ______, and usually lasts about _____
mitosis
one hour
_____ phase is where there is the most variability among cell types
G1
The length of _______ determines the length of the cell cycle, with ____ being the greatest determinant
interphase
G0
The checkpoint at ____ is to ensure if the environment is favorable for division
G1
The checkpoint at ___ is to check is the environment is favorable AND that DNA is duplicated; and the cell with undergo apoptosis if not
G2
The checkpoint at ______ is to ensure the chromosomes are attached to the spindle
metaphase
_______ are normal cellular genes that function in cell proliferation
protooncogenes
Protooncogenes have a _____ mutant phenotype; cellular transformation occurs with a mutation in ____ allele
dominant
one
A mutated protooncogene is called a ______
oncogene
______ _____ _____ are anti proliferative genes
tumor supressor genes
Tumor supressor genes have a _____ mutant phenotype; loss of expression in _____ allele leads to uncontrolled cell division
recessive
both
_____ _____ are signals for proliferation, usually several work in concert to stimulate cell division; do not induce division, bind to specific cell receptors thus involved in signal transduction pathways, PDGF is the model
growth factors
How cells respond to PDGF (platelet derived growth factor):
increase in intracellular ____ ions
reorganization of ___ stress fibers to facilitate attachment
activation and nuclear translocation of _____ _____
____ synthesis and _____ division
calcium actin transcription factors DNA cell
Growth factors: PDGF
growth factor + growth factor receptor –> receptor _________
oligomerization
Growth factors: PDGF
receptor oligomerization —> receptor ____ activation (intrinsic = ______; extrinsic = ______)
PTK (protein tyrosine kinase)
part of receptor
separate protein that associates with receptor
Growth factors: PDGF
receptor PTK activation –> ______ of PTK moiety —> docking sites form
phosphorylation
Growth factors: PDGF
once docking sites form —> _______ of signaling enzymes —> activation of _____ _____
recruitment signal transduction (ST) elements
PTKs transfer a __________ group of ATP to _________ residues on target substrate proteins
γ-phosphate
tyrosine
Tyrosine phosphorylation, which is a covalent modification of proteins, provides a _________ and ________ (by the action of protein tyrosine phosphatases) mechanism of modifying the enzymic activity of target proteins.
rapid
reversible
The importance of PTKs in cell _______ and ________ function is illustrated by the defects resulting from _________ in these genes occurring in humans
proliferation
effector
mutations
Mutations in ______ can result in severe combined immunodeficiency (SCID) due to severe abnormalities in T cell development, X-linked agammaglobulinemia, an immunodeficiency characterized by lack of IgG antibody production, chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and occasionally in acute myeloid leukemia (AML)
PTK
Docking sites created by PTK can lead to recruitment of _______ _______ enzymes, specifically PLC and GAP
downstream signaling
PDGF is a ______ ______ receptor, it involves ________ and _____-____ cascades, it is involved in the recruitment of _____, the second messengers are _____ and ______, and its molecular switch is ______
membrane bound phosphatidylinositol Ras-MAPK PLC IP3 DAG Ras
If Ras is on then _____ undergoes uncontrolled division; because Ras regulates the _____ pathway, which is involved in the regulation of DNA synthesis and cell division (TF activation)
MAPK
Grb2 and Sos recruit _____ and is inactive due to GDP; _____ promotes the activation of _____ whereas ____ inactivates ____ by stimulating its intrinsic ______ activity
Ras Sos Ras GAP Ras GTP
______ of all tumors have mutation in ____ that render it constituently active
30%
Ras
With cytokines; hemopoietic receptors are ____ _____, JAKs couple the receptor directly to ________, STATs ________ in cytoplasm then translocate to the nucleus to activate _______
membrane bound
transcription
phosphorylated
transcription
True or False The following are key regulators of the cell cycle: cyclin/CDK complexes retinoblastoma protein (Rb) p53 (tumor supressor gene) CDKIs E2F family of Tfs
True
Cyclin/CDK (cyclin dependent kinses)
the _______ of cyclins via mRNA/protein levels
the _______ on CDKs via phosphorylation and CDKIs
A CDK can have _____ activities when interacting with different cyclins
abundance
activity
differing
Growth factors usually exert effects between the onset of ____ and the _____ _____ (late G1)
G1
restriction point
Once past the restriction point, the rest of the phases up to mitosis are ______, but not ______
committed
unregulated
_________ is the gatekeeper of the restriction point
retinoblastoma (Rb)
In early G1, ______ prevents transcription factors, closer to the restriction point _________ phosphorylates _____; hyperphosphorylated _____ releases TFs allowing the cycle to pass the restriction point
Rb
cyclin D-CDK4
Rb
Rb
If damage is detected during the cell cycle, ________ induces unphosphorylation of Rb
CDKI p21
In S phase, ______ monitors for damage
p53
While committed, the cell cycle can be _____ ____ beyond the restriction point if DNA needs to be repaired
slowed down
Irreparable damage during cell cycle = ________
apoptosis
In apoptosis; inappropriate cell death can lead to _________ disorders, subversion of cell death leads to _____ or ______ disease
degenerative
cancer
autoimmune
In apoptosis, caspases are _________,
______ is a regulator and its antiapoptotic
proteases
Bcl-2
Cell death domains attract ________ which induce _____ _____ activation cascade, causing apoptosis; survival factors stimulate ______ which inactivate _______ allowing the cell to survive
procaspases
proteolytic caspase
Bcl-2
caspases
Hyperphosphorylation and inactivation of Rb leading to deregulated malignant cell proliferation leads to ______ cancer(s)
breast
Loss of Rb control of cell cycle, leading to deregulated malignant cell proliferation leads to _____ cancer(s)
retinoblastoma(s)
Loss of Rb control of cell cycle leads to ______ cancer(s)
cervical
Loss of inhibition of cyclin D-CDK4/6 complexes, resulting in inappropriate hyperphosphorylation and inactivation of Rb leads to ______ cancers
many; a variety of tumor cells
Loss of inhibition of cyclin D-CDK4/6 complexes, resulting in loss of Rb control of cell cycle leads to _______ cancer(s)
melanomas
Each tumor originated from a _____ mutant cell(s) that outgrew its neighbors
single
The normal mutation rate = _____/cell divison
10 to the 6th
Several _____ mutations have to occur over a lifetime, which is why cancer increases exponentially with ____; usually ___-___ mutations required
rare
age
3-7
90% of human cancers are ________
carcinomas
Cancer of the epithelial tissue type is _______
carcinoma
Cancer of the connective tissue or muscle tissue type is ________
sarcoma
Cancer of the hematopoietic tissue type is ________
leukemia
_______ were first identified as viral genes that infect normal cells and lead to transformation
oncogenes
C-Src protooncogene is a ______ involved in normal cell growth (removes introns)
PTK
Viral oncogene is a _____ _____ of normal cellular gene
mutated homolog
A gene can come under control of a _______ ______ or _____ that a virus introduces into the genome
constitutive promoter
enhancer
Insertion of a ______ can cause activation of a protooncogene
retrovirus
85% of human tumors arise from _____ _____ or ______ in oncogenes
point mutations
deletions
In _______ cancer, 50% of these tumors had an activating point mutation in a Ras oncogene, and 75% of these cancers had an inactivating mutation in p53; loss of the DNA-damage sensing function of p53 allows the cells to accumulate, at a rapid rate (these mutations appear to be the rate-limiting steps)
colorectal
_______ are extremely rare; the hereditary form results from a deletion or loss of function mutation of the Rb gene in _____ cell
In the non-hereditary form, both copes are defective in cancer forms
retinoblastomas
every
The most common genetic lesion found in human cancer is in ____
p53
Individuals with only one functional _____ are predisposed to sarcoma, lung, breast, larynx, and colon cancers, brain tumors, and leukemias
p53
True or False
Signs and symptoms of oral cancers can be;
white or red patches in the mouth, a mouth sore that doesn’t heal, bleeding, loose teeth, painful swallowing, a lump in the neck, and an earache
True
True or False
Oral cancer count for roughly 20% of all malignant lesions worldwide
False; only about 5%
True or False
The 5-year survival rate of oral cancer is ~80%
False; the survival rate is only 50% mostly due to late detection
The majority (96%) of oral cancers are ________
carcinomas
Most oral cancers are _______ cell carcinomas that tend to ______ ______
squamous
spread quickly
True or False
Oral cancers rank #10 in the global cancer burden
False; they rank at #5
True or False
Oral cancers may require surgery, radiation, or chemotherapy (or a combination of them all)
True
True or False
Smoking/tobacco use is associated with nearly 90% of all oral cancer cases
False; it is associated with ~75%
True or False
Besides smoking/tobacco use, other risk factors for oral cancer include heavy alcohol use, HPV, chronic irritation, immunosuppressants, and poor dental/oral hygiene
True; most cancers arise from a combination of different risk factors
________ converts nicotine to cotinine which is glucuronidated and then enters the bloodstream
CYP2A6 (cytochrome P450s)
in the body, ______ can be oxidized and will act as an alkylating agent, leading to DNA damage
amines
_____ are ROS
NOs
_____ mutation = oral cancer from smoking
GST
Extra-hepatic metabolism of alcohol to acetaldehyde is particularly shown to occur in oral cavity, acetaldehyde is __________, and increases ______ permeability; heterozygous genotype substantially predisposed to esophageal cancer
mutagenic
mucosal
______ interferes with DNA repair enzymes; oral microflora produces a considerable amount (streptococci)
acetaldehyde
______ decreases secretions from parotid glands
alcohol
There is mounting evidence that _____ in ______ is causing a predisposition to oral cancer
alcohol in mouthwash
____ is more often a cause of oral cancer than smoking
HPV
HPV-16 immortalized cells express higher _____ enzymes; significantly higher concentrations of the _______ compound derived from nicotine in the cervical mucosa of smokers; thus more likely to have carcinogenic nitrosamines produced in those cells
P450
butanone
HPV E6 interacts with ____ preventing commitment to apoptosis
p53
HPV E7 binds to ___ preventing damaged cell growth stoppage
Rb
HPV E5 inhibits ATPS involved in ________ function, delaying endosomal litigation, delaying the response to ____
lysosomal
ROS
