Smith - Cellular Homeostasis Flashcards by Courtney Kast

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

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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

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In the cell cycle, the cell first ______ its contents, then ______ into ____ _____ ______

duplicate
divides
two daughter cells

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The division part of the cell cycle is called ______, and usually lasts about _____

mitosis

one hour

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_____ phase is where there is the most variability among cell types

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The length of _______ determines the length of the cell cycle, with ____ being the greatest determinant

interphase

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The checkpoint at ____ is to ensure if the environment is favorable for division

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The checkpoint at ___ is to check is the environment is favorable AND that DNA is duplicated; and the cell with undergo apoptosis if not

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The checkpoint at ______ is to ensure the chromosomes are attached to the spindle

metaphase

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_______ are normal cellular genes that function in cell proliferation

protooncogenes

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Protooncogenes have a _____ mutant phenotype; cellular transformation occurs with a mutation in ____ allele

dominant

one

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A mutated protooncogene is called a ______

oncogene

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______ _____ _____ are anti proliferative genes

tumor supressor genes

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Tumor supressor genes have a _____ mutant phenotype; loss of expression in _____ allele leads to uncontrolled cell division

recessive

both

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_____ _____ 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

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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

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Growth factors: PDGF

growth factor + growth factor receptor –> receptor _________

oligomerization

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Growth factors: PDGF

receptor oligomerization —> receptor ____ activation (intrinsic = ______; extrinsic = ______)

PTK (protein tyrosine kinase)
part of receptor
separate protein that associates with receptor

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Growth factors: PDGF

receptor PTK activation –> ______ of PTK moiety —> docking sites form

phosphorylation

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Growth factors: PDGF

once docking sites form —> _______ of signaling enzymes —> activation of _____ _____

recruitment
signal transduction (ST) elements

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PTKs transfer a __________ group of ATP to _________ residues on target substrate proteins

γ-phosphate

tyrosine

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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

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The importance of PTKs in cell _______ and ________ function is illustrated by the defects resulting from _________ in these genes occurring in humans

proliferation
effector
mutations

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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

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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

HPV E5 inhibits ATPS involved in ________ function, delaying endosomal litigation, delaying the response to ____

lysosomal | ROS