BIOL 4004 Final Exam

Weeks 9-14 quizlets from class

A form of programed cell death in which a "suicide" program is activated within an animal cell. This leads to rapid cell death mediated by intracellular proteolytic enzymes called caspases.

Apoptosis

A form of programmed cell death in which the damaged cell bursts, releasing intracellular molecules into the extracellular space, potentially triggering immune or inflammatory responses.

Cell necrosis

A family of signal protein receptors containing eight members, including Fas and TNF. These proteins contain an extracellular ligand-binding domain, a single transmembrane domain, and an intracellular death domain required to activate the extrinsic pathway of apoptosis.

TNF (tumor necrosis factor) family of signal proteins

Intracellular proteases that are involved in mediating the intracellular events of apoptosis.

Caspases

Pathway of apoptosis triggered by cell injury, DNA damage, a lack of oxygen, a lack of extracellular survival factors, or in response to intracellular developmental signals. Also known as the mitochondrial pathway of apoptosis.

Intrinsic pathway of apoptosis

A trimeric ligand that activates its trimeric cell-surface death receptor triggering the extrinsic pathway of apoptosis. This transmembrane protein is expressed on multiple cell types such as killer (cytotoxic) lymphocytes.

Fas ligand

Receptors that bind extracellular death ligands, but lack the intracellular death domains necessary for the binding of an adaptor protein and activation of the amplifying proteolytic cascade.

Decoy receptors

Apoptotic caspases that begin the apoptotic process, activating the executioner caspases.

Initiator caspases

A main effector Bcl2 family protein of the intrinsic pathway of apoptosis that is bound to the mitochondrial outer membrane even in the absence of an apoptotic signal. Is usually activated by pro-apoptotic BH3-only proteins.

Bak

A mammalian inhibitor of apoptosis protein that is encoded on the X chromosome and located in the cytosol. It binds to and inhibits initiator caspase-9 as well as executioner caspase-3 and caspase-7. This protein sets an inhibitory threshold these caspases must overcome to trigger apoptosis.

XIAP

A negatively charged phospholipid that is normally confined to the cytoplasmic leaflet of the lipid bilayer of the plasma membrane. In apoptotic cells, it accumulates in the outer leaflet, where it serves as an "eat me" signal to the neighboring phagocytic cells.

Phosphatidylserine

Complex in which initiator caspases interact and are activated after extracellular ligands bind to cell-surface death receptors in the extrinsic pathway of apoptosis.

DISC (death-inducing signaling complex)

A main effector Bcl2 family protein of the intrinsic pathway of apoptosis that is located mainly in the cytosol. It translocates to the mitochondria only after activation, usually by activated pro-apoptotic BH3-only proteins.

Bax

Transmembrane receptor proteins that can signal the cell to undergo apoptosis when it binds its extracellular ligand.

Death receptors

A serine-threonine kinase that acts in the PI-3-kinase Akt intracellular signaling pathway that is also known as protein kinase B (PKB). This kinase is activated by the binding of a survival factor. The active kinase phosphorylates and inactivates the BH3-only protein Bad.

Akt

A homotypic protein interaction domain found on death receptors that is composed of a bundle of six α-helices and related in sequence and structure to the caspase recruitment domain (CARD). This domain is required for death receptors to activate the extrinsic pathway of apoptosis.

Death domain (DD)

A soluble component of the electron-transport chain. When released into the cytosol from the mitochondrial intermembrane space, it initiates apoptosis.

Cytochrome c

A homotypic protein interaction domain found on Apaf1 that is composed of a bundle of six α-helices and related in sequence and structure to the death domain (DD). When exposed on Apaf1, this domain recruits an inactive caspase-9 monomer.

CARD (caspase recruitment domain)

A homology domain that is found in all members of the Bcl2 family. The Bcl2 family proteins differ in the number of these domains that they contain (BH1, BH2, BH3, BH4).

BH domain (Bcl2 homology)

Trimeric transmembrane death receptors that initiate apoptosis when they bind their extracellular trimeric ligand.

Fas death receptors

An intracellular blocking protein that resembles an initiator caspase, but lacks the protease domain necessary for the activation of the proteolytic cascade. This protein competes with initiator caspases for binding sites on DISC, but since it cannot cleave its partner it is unable to form stable activated initiator caspases.

FLIP

A BH3-only protein that links the extrinsic and intrinsic pathways of apoptosis. When the extrinsic pathway is activated, the initiator caspase-8 cleaves this protein to produce a truncated active version. This active version translocates to the mitochondria and inhibits anti-apoptotic Bcl2 proteins.

Bid

A small intracellular adaptor protein containing death domains that connects Fas receptor to the caspase cascade.

FADD (Fas-associated death domain)

Intracellular protein inhibitors of apoptosis that bind to and inhibit caspases.

IAPs (inhibitors of apoptosis)

The change in the outer mitochondrial membrane that releases cytochrome c and other soluble proteins from the intermembrane space into the cytosol. This is a critical step in the intrinsic pathway of apoptosis.

Mitochondrial outer membrane permeabilization (MOMP)

An adapter protein of the intrinsic apoptotic pathway. When it binds cytochrome c, it oligomerizes to form an apoptosome.

Apaf1 (apoptotic protease activating factor-1)

Pro-apoptotic proteins that contain BH1, BH2, BH3 domains that form aggregates in the mitochondrial outer membrane and trigger the release of cytochrome c and other intermembrane-space proteins.

Effector Bcl2 family proteins

Apoptotic caspases that catalyze the widespread cleavage during apoptosis that kill the cell.

Executioner caspases

Proteins that are produced in response to various apoptotic stimuli and by binding to inhibitory anti-apoptotic proteins, prevent their binding to a caspase. This therefore blocks the inhibition of apoptosis provided by IAPs.

Anti-IAP proteins

A heptamer of Apaf1 proteins that forms upon activation of the intrinsic apoptotic pathway. It recruits and activates initiator caspases that will activate downstream executioner caspases to induce

Apoptosome

Pathway of apoptosis triggered by the binding of extracellular signals to transmembrane death receptors.

Extrinsic pathway of apoptosis

A pro-apoptotic protein BH3-only protein that when unphosphorylated, promotes apoptosis by binding to and inhibiting anti-apoptotic Bcl2. When phosphorylated, this protein releases bound Bcl2.

Bad

Extracellular signal molecules that inhibit apoptosis. They act as social controls to ensure that individual cells survive or die, depending on what is best for the organism as a whole.

Survival factors

An inactive, soluble monomeric version of the initiator caspases found in the cytosol.

Procaspase

Anti-apoptotic family protein of the outer mitochondrial membrane that binds and inhibits pro-apoptotic Bcl2 family proteins. Prevents inappropriate activation of the intrinsic pathway of apoptosis. This protein is the first family member discovered, known as B cell lymphoma-2.

Bcl2

Family of intracellular proteins that either promote or inhibit apoptosis by regulating the release of cytochrome c and other mitochondrial proteins from the intermembrane space into the cytosol.

Bcl2 family

Largest subclass of Bcl2 family proteins that are produced or activated in response to an apoptotic stimulus. These proteins promote apoptosis mainly by inhibiting anti-apoptotic proteins in the Bcl2 family.

BH3-only proteins

Anti-apoptotic Bcl2 family protein of the outer mitochondrial membrane that binds and inhibits pro-apoptotic Bcl2 family proteins. Prevents inappropriate activation of the intrinsic pathway of apoptosis. This protein is known as B cell lymphoma-2 extra-large.

BclxL

Proteins on the cytosolic surface of the outer mitochondrial membrane containing all four BH domains that bind and inhibit pro-apoptotic effector Bcl2 family proteins. They also help prevent inappropriate activation of the intrinsic pathway of apoptosis.

Anti-apoptotic Bcl2 family proteins

Type of programmed cell death in which the damaged cell bursts open, releasing intracellular molecules into the extracellular space, potentially triggering immune or inflammatory responses.

Necrosis

A cell that is invasive and/or able to undergo metastasis; this type of tumor is a cancer.

Malignant

A secondary tumor at sites in the body additional to that of the primary tumor. They result from cancer cells breaking loose, entering blood or lymphatic vessels, and colonizing separate environments.

Metastases

A highly regulated process that allows epithelial cells to lose their characteristic polarity and adhesiveness and take on a mesenchymal phenotype including enhanced migratory behavior.

Epithelial-mesenchymal transition (EMT)

A normal gene, usually concerned with the regulation of cell proliferation, that can be converted into a cancer-promoting gene by mutation.

Proto-oncogene

The process by which normal cells become malignant.

Transformation

The observation that most cancer cells predominantly produce energy by glycolysis followed by fermentation of pyruvate to lactic acid. While normal cells use this form of energy production only under the oxygen-limiting (anaerobic) condition, cancer cells metabolize glucose in this manner even in the presence of sufficient oxygen. Also known as aerobic glycolysis.

Warburg effect

In cancer development, when cancer cells develop more slowly, potentially taking years to cause symptoms and may be relatively harmless. Initial phase seen in CML and cervical cancer.

Chronic phase of cancer

Cancers arising from epithelial cells; the most common cancers in humans.

Carcinoma

Alterations in the pattern of gene expression without a change in the DNA sequence.

Epigenetic changes

Abnormally increased spontaneous mutation rate, such as occurs in cancer cells.

Genetic instability

A rare cancer caused by human herpesvirus HHV-8 and found at much higher rates in immune-compromised individuals infected with HIV.

Kaposi's sarcoma

Mutations that have occurred due to the genetic instability of the cancer, but are irrelevant to the development of the disease.

Passengers of cancer

A rare type of human cancer arising from cells in the retina of the eye that are converted to a cancerous state by an usually small number of mutations. Studies of this disease led to the discovery of the first tumor suppressor gene.

Retinoblastoma (cancer)

A physical or chemical agent that permanently changes genetic material (DNA) within an organism. This increases the frequency of mutations above the natural background level; and is commonly tested for using an Ames test.

Mutagen

Normal cells are inhibited from moving and dividing when cell cultures reach confluence (the cells are touching). Transformed cells continue moving and dividing.

Contact inhibition

A DNA tumor virus that is the cause of human warts and most cervical cancers.

Papillomaviruses

A gene that appears to help prevent formation of cancer because it normally inhibits cell division. A recessive loss-of-function mutation in such genes favors the development of cancer.

Tumor suppressor gene

Phenomenon observed in primary cell cultures in which cell proliferation slows down and finally irreversibly halts.

Replicative cell senescence

Transcription regulatory protein that is activated when a cell is stimulated to grow and divide by extracellular signals. It activates the transcription of many genes, including those that stimulate cell growth.

Myc

Cell growth, proliferation, and survival that is no longer dependent upon attachment to a substratum.

Anchorage-independent growth

Variety of DNA viruses that can cause tumors by interfering with controls of the cell cycle and apoptosis.

DNA tumor viruses

Process by which tumor cells are able to survive and proliferate in a new environment. This is the rate limiting step in metastasis.

Colonization

How differentiating cells begin; cells that initially proliferate extensively and eventually differentiate into one of several possible specialized cell types.

Transit amplifying cells

A tumor suppressor protein involved in the regulation of cell division. Its normal activity is to regulate the cell cycle by binding to and inhibiting E2F proteins, thus blocking progression to DNA replication and cell division.

Rb protein (retinoblastoma protein)

The analysis of disease frequency in populations. The principal tool for detecting possible environmental causes of cancer.

Epidemiology

A mutation that causes the complete or partial absence of normal function.

Loss-of-function mutation

Test in which special strains of bacteria are used to evaluate the potential of chemicals to cause cancer.

Ames test

An altered gene whose product can act in a dominant fashion to help make a cell cancerous. Typically, it is a mutant form of a normal gene involved in the control of cell growth or division.

Oncogene

A rare cancer of the bone marrow that causes an increased number of white blood cells in the blood. Genetically, it is due to a translocation that produces the Philadelphia chromosome which forms a chimeric protein called Bcr-Abl. This creates a new protein kinase that phosphorylates proteins that wildtype Abl kinase does not.

Chronic myelogenous leukemia (CML)

Slow-dividing, self-renewing cells whose division produces new versions of themself and cells that enter a differentiation pathway.

Stem cells

A tumor at the original site at which a cancer first arose; are formed due to the proliferation of a single mutant cell.

Primary tumor

The formation of new blood vessels from pre-existing blood vessels. A process that aids metastasis by attracting a dense supply of blood.

Angiogenesis

Noncancerous cell lines that are usually derived from mouse fibroblasts. They contain mutations that predispose them to cancer; as a result, the addition of a single oncogene can be enough to cause transformation.

Tester cell lines

Secondary tumors begin as these small clumps of cells.

Micrometastases

A cell with an altered phenotype that behaves in many ways like a cancer cell (aka, has unregulated proliferation and anchorage-independent growth in culture).

Transformed

A tumor that is self-limiting in growth and non-invasive; a small local mass that has not yet spread.

Benign

Rare cancer cells capable of dividing indefinitely.

Cancer stem cells

In cancer development, when cells are less mature and fast-developing and become dysfunctional cells that are malignant. Generally a later phase seen in CML and cervical cancer.

Acute phase of cancer

First animal virus implicated in cancer; discovered 100 years ago in chickens where it causes connective tissue sarcomas.

Rous sarcoma virus

A substance capable of causing cancer; a substance that increases the rate of cancer.

Carcinogen

Tumor suppressor genes involved in repairing DNA double-stranded breaks.

Brca1 and Brca2

A drug that inhibits the activity of the chimeric Bcr-Abl protein in chronic myelogenous leukemia patients.

Imatinib (Gleevec)

A mutation that produces a new trait or causes a trait to appear in inappropriate tissues or at inappropriate times in development.

Gain-of-function mutation

A transcription regulatory protein that is activated by DNA damage and is involved in blocking further progression through the cell cycle until the damage can be repaired. The gene encoding this protein is a tumor suppressor gene that is mutated in about half of human cancers.

p53

A tumor that develops at a different site from the original by metastasis.

Secondary tumor

A subclass of mutations that lead to genetic instability.

Genome maintenance genes

A small family of proto-oncogenes that are frequently mutated in cancers, each of which produces a monomeric GTPase.

Ras

Mutations that are defects that factor in the development of the cancer disease.

Drivers of cancer

Genes whose alteration contributes to the causation or evolution of cancer by driving tumorigenesis.

Cancer critical genes

A type of cancer in which a translocation brings the Myc gene under the control of regulatory sequences that normally govern the production of antibodies in B lymphocytes, resulting in excessive proliferation of B cells.

Burkitt's lymphoma

Bacteria that causes stomach ulcers and is a major factor in stomach cancer.

Helicobactor pylori

A cancer of the connective tissue.

Sarcoma

RNA-containing virus that replicates in a cell by first making an RNA-DNA intermediate and then a double-stranded DNA molecule that becomes integrated into the cell's DNA.

Retrovirus

Extracellular signal proteins that can stimulate a cell to grow (increase cell mass). These proteins have other functions as well, including stimulating cells to survive or proliferate.

Growth factors

A DNA tumor virus that infects the basal cells of the cervical epithelium causing human warts and is a causative factor in cervical cancer.

Human Papillomavirus (HPV)

An extracellular signal molecule that stimulates cells to progress through the cell cycle (proliferate).

Mitogen

Stage of mitosis during which chromosome segregation occurs as chromosomes move towards the 2 spindle poles.

Anaphase A

Protein kinases that must be complexed with a cyclin protein in order to be functional. Different complexes trigger different steps in the cell cycle by phosphorylating specific target proteins.

Cyclin-dependent protein kinases (Cdks)

A RhoA GEF (guanine nucleotide exchange factor) that activates RhoA by stimulating the release of GDP and binding of GTP to RhoA. This GEF is localized to the cell division site.

Ect2

Phase during which cells undergo nuclear division.

Mitosis (M phase)