Cell cycle, apoptosis, and stem cells

Question 1

G0

Answer 1

Vast majority of cells are in this resting phase at any given time.

Question 2

5 components of cell cycle control system

Answer 2

1. Retinoblastoma protein (pRb) 2. Cyclins 3. Cyclin-dependent kinases 4. CDK inhibitors (CDKI) 4. Transcription factors

Question 3

Retinoblastoma protein (pRb)

Answer 3

Tumor suppressor protein encoded by Rb1. When hypophosphorylated inhibits cell progression, when phosphorylated it is inactivated and allows cell to continue to the transition from M to G1 phase. Very important in preventing excessive cell growth/proliferation.

Question 4

Phosphorylation of pRb

Answer 4

Carried out by cyclins and CDKs. Becomes more and more phosphorylated throughout cell cycle and then hypophosphorylated after mitosis.

Question 5

Retinoblastoma (disease)

Answer 5

Cancer of the eye which originates in the retina. Caused by mutation in both alleles of Rb1 protein becomes inactivated. Can be inherited or through spontaneous mutation. Unknown why effects are not systemic.

Question 6

Importance of appearance/disappearance of cyclins

Answer 6

Phosphorylation is easily reversible, but proteolysis (of cyclins) is not. Cyclin gene transcription helps regulate cell cycle control.

Question 7

2 classes of regulatory molecules which control cell cycle

Answer 7

1. Cyclins 2. Cyclin-dependent kinases (CDKs)

Question 8

Cyclins

Answer 8

Regulatory subunit. Sequential activation ensures correct timing and ordering of cell cycle events. Synthesized at specific stages of cell cycle in response to molecular signals.

Question 9

Cyclin-dependent kinases (CDKs)

Answer 9

Catalytic subunit activated when bound to a cyclin. Constitutively expressed in cells.

Question 10

Hyperproliferation

Answer 10

Caused by hyperactivity of CDKs, seen in neoplasms

Question 11

Cyclin C overexpression

Answer 11

Found in neurons and astrocytes in Alzheimer’s disease

Question 12

Abnormal Cyclin E expression

Answer 12

Seen in premalignancy and malignancy in lungs. Negative marker for prognosis.

Question 13

Overexpression of Cyclin A

Answer 13

Found in tumors and cancer cell lines. Accelerates pRb phosphorylation, promotes entry into S-phase. Associated with ability of cells to grow in suspension.

Question 14

G1/S checkpoint

Answer 14

Critical checkpoint (restriction point). Prior to checkpoint cell depends on external stimuli to progress. After checkpoint cell becomes independent of external mitogenic stimuli and can complete cell division cycle autonomously.

Question 15

p53

Answer 15

Tumor suppressor protein and transcription factor has role in G1/S and G2/M. Guards genome against attack by DNA damage.

Question 16

3 functions of p53

Answer 16

1. Can activate DNA repair when damaged 2. Can induce growth arrest by holding cell cycle at the G1/S checkpoint (if held long enough time for DNA repair so cell can continue through cycle) 3. If damaged DNA cannot be repaired can initiate apoptosis

Question 17

p53 in cancer

Answer 17

Protects against tumor development. One target inhibits cyclin E and cyclin A/CDK complexes to cause cell cycle arrest in G1. If mutated or missing one copy, particularly in combination with another mutation (like Ras), have high risk of developing tumors.

Question 18

p53 and Ras

Answer 18

p53 affects transcription in one group of genes and Ras affects another group. Together synergistically regulate subset of genes known as cooperation response genes (CRGs) which are crucial mediators of tumor formation.

Question 19

1. Apoptosis vs. 2. necrosis

Answer 19

1. Programmed cell death 2. Traumatic cell death with spillage of cell contents.

Question 20

2 mechanisms controlling apoptosis

Answer 20

1. Intracellular signals (lack of nutrients, low oxygen, heat) 2. Extracellular signals (hormones, toxins, cytokines, growth factor withdrawl)

Question 21

Cytokines in apoptosis

Answer 21

Pro-apoptotic cytokines control apoptosis by direct signal transduction.

Question 22

Caspase activation pathway

Answer 22

Tumor necrosis factor (TNF) produced by macrophages and Fas ligand (transmembrane protein which binds to its receptor and induces apoptosis) activate pro-apoptotic enzymes called caspases than activate DNases and degrade intracellular proteins

Question 23

2 abilities of stem cells

Answer 23

1. Self-renewal through mitosis (indefinitely) 2. Differentiate into specialized cell types and cen be totipotent or pluripotent

Question 24

Totipotent cells

Answer 24

Ability to differentiate into all cell types and give rise to an entire organism (zygote is perfect example)

Question 25

Pluripotent cells

Answer 25

Potential to differentiate into any of the fetal or adult cell types but they themselves cannot give rise to an embryo or entire organism (cannot differentiate into extrafetal tissues such as placenta)

Question 26

Progenitor cells

Answer 26

Unlike stem cells, cannot divide and reproduce themselves indefinitely

Question 27

Multipotent cells

Answer 27

Progenitor cells that can give rise to multiple, but limited, cell lineages.

Question 28

Unipotent cells

Answer 28

Progenitor cells that give rise to only one cell/tissue type.

Question 29

3 types of stem cells

Answer 29

1. Embryonic 2. Adult 3. Induced pluripotent

Question 30

Embryonic stem cells

Answer 30

Derived from inner cell mass of blastocyst in vitro prior to implantation. Can cause teratomas upon implantation into host.

Question 31

Teratoma

Answer 31

Often benign encapsulated tumor consisting of tissues resembling endoderm, mesoderm, ectoderm (nails, skin, teeth, hair)

Question 32

Adult stem cells

Answer 32

Example is the hemapoietic stem cell from bone marrow or umbilical cord. Can be purified from peripheral blood after mobilization from bone marrow through influence of colony-stimulating factor (G-CSF).

Question 33

Induced pluripotent stem cells

Answer 33

Somatic (body cells as opposed to germ cells) which are reprogrammed to be pluripotent

Question 34

2 ways to induce pluripotent stem cells

Answer 34

1. Inducing a forced expression of specific genes through transfection of adult somatic cell with a vector (often induces cancer) 2. Using purified proteins to transform adult cells into embryonic-like cells

Question 35

Microchimerism

Answer 35

Bidirectional trafficking and persistence in small numbers of allogenic cells (from another individual). Donated cells are genetically different from host.

Question 36

Freemartin

Answer 36

Example of microchimerism. Female calf that is infertile due to influence of male hormones and blood components from male twin brother who shared the placents in utero

Question 37

Fetal microchimerism

Answer 37

Most common human form. Between mother and fetus whereby cells from fetus travel through placenta to the mother. May estabilsh cell lineages and multiply. Maternal microchimerism can also occur but rare.

Question 38

Clinical significance of microchimerism good/bad

Answer 38

Bone marrow transplants from child to mother show reduced graft vs host reaction (immunotolerance). More fetal cells found in maternal circulation when fetus was aneuploid.