Day 3, Lecture 2 (Aug 24): Biology of Cells II- Cell Cycle/Differentiation Molecular and Cellular Systems

Question 1

Destroying Angel

Answer 1

• Amatoxin:
  
  • Thermostable, rapid absorption, irreversible damage to liver and kidney
  • Perforate plasma membranes causing organelle leakage. Also inhibits RNA polymerase II/III (stops protein synthesis). Cells die, liver dissolves
• symptoms: coughing, headache, shortness of breath, vomiting, cramps, diarrhea, delirum, convulsions, death

Question 2

Cirrhosis

Answer 2

• Long term liver damage causing cell death and scarring
• causes:
  
  • Alcohol, Hepatitis (B or C), non-alcoholic fatty liver disease
• Symptoms
  
  • Tired, itchy, leg swelling, jaundice, ascites
• Leads to:
  
  • hepatic encephalopathy (confusion/coma), bleeding, liver cancer, death

Question 3

What three concepts underlie the unity of life

Answer 3

1. Cell theory
   
   • A cell is the fundamental unit of organismal structure/function
   • all cells come from cells
   • Cells maintain/transfer hereditary information determining fate
2. Bioenergetics (energy flow and transformation)
   
   • cell metabolism converts nutrients into energy to do work
3. Evolution

Question 4

Degrees of organization

Answer 4

• Organs/structures formed from tissues
• Tissues from cells
• Cells of organelles
• Organelles from molecules
• Molecules from atoms

Question 5

What are the four fates of cells

Answer 5

• Survival
• Division
• Differentiate
• Die (apotosis or necrosis)

Question 6

Liver cell types

Answer 6

• Hepatocytes
  
  • Glycolysis, gluconeogenesis, produce bile
• Kupffer cells
  
  • macrophages protect from pathogens and cancer cells
• Stellate cells
  
  • Store Vitamin A
• Sinusoidal Cells
  
  • Endothelial Cells lining sinuses (space between hepatocytes). Regulate Molecule passage

Question 7

The ___ is the smallest fundamental replicating unit

Answer 7

Cell

Question 8

Cells organize into ___ and adopt specific fates

Answer 8

tissues

Question 9

Cell fate determined by

Answer 9

• communication with other cells, microenvironment
• Receiving, transmitting,interpreting multiple signals
• self evaluation
• Alters cell cycle, gene expression, cytoskeleton, etc.

Question 10

Disrupted cell fate decisions underlie ____, ____, and _____ malfunctions (e.g. poisoning and cirrhosis)

Answer 10

Cellular, tissue, and organ

Question 11

Tuberous Sclerosis

Answer 11

• Rare (1/8000) multi-system genetic disease.
• Symptoms
  
  • benign tumors, seizures, intellectual disability, skin abnormalities, lung/kidney disease
• Inappropriate cell proliferation forming hamartia (malformed tissue), hamartomas (benign growths like facial angiofibroma)
• Mutational loss of both TSC1/2 alleles prevents tumor suppressing function; ie Knudson “two hit” hypothesis
  
  • Sporadic:
    
    • 2 acquired mutations
  • Hereditary:
    
    • 1 inherited, 1 acquired mutation

Question 12

Familial Adenomatous Polyposis

Answer 12

• Genetic disease benign polyps in large intestine epithelium. Blood in stool, anemia (iron loss). Malignant transformation into colon cancer if untreated
• Mutation (1 or 2 hit) of adenomatous polyposis coli (APC), a tumor suppressor gene regulating ß-catenin
  
  • ß-catenin regulates cell-cell adhesion and gene transcription controlling proliferation
  • further mutations (e.g. in p53 or kRAS) to APC-mutated cells lead to cancer

Question 13

Stroke

Answer 13

Question 14

Myocardial Infarction (heart attack)

Answer 14

Question 15

Cell cycle progression controlled by highly regulated ____

Answer 15

CDKs

Question 16

Differentiation, senescence, and apoptosis all require ordered cell cycle exit to G0 before Restriction point

Question 17

Question 18

Extracellular signals target cell cycle machinery to

Answer 18

communicate cell fate

Question 19

_____ is a key period for making cell fate decisions

Answer 19

Restriciton point

Question 20

do multiple signaling inputs (positive and negative) converge on the Restriction point to determine cell fate

Answer 20

yes

Question 21

The Restriction point

Answer 21

Question 22

Question 23

Question 24

Question 25

Question 26

Question 27

Question 28

Question 29

Question 30

Question 31

Signals activate G1 CDKs to continue the cell cycle and become mitogen independent or inhibit CDKs to ____

Answer 31

• exit and adopt an alternative fate

Question 32

Adipogenesis

Answer 32

Question 33

Adipogenesis promotes _____

Answer 33

• G1 progession
  
  • Excess calories/adipocyte size activate growth factors, adipogenesis in pre-adipocytes (undifferentiated fibroblasts)
  • Signal transduction activates G1 components driving R point progression

Question 34

Question 35

Question 36

Question 37

Mitogenic control of cyclin D-CDK4

Answer 37

• Cyclins and CKDs have to be brought together and then phosphorylated to become active

Question 38

Answer 38

Question 39

G1 progression and the switch to mitogen independence

Answer 39

• Mitogens bind to the cell-surface receptors to initiate intracellular signaling pathways.
• ex. A small GTPase Ras will activate MAP kinase cascade, leading to increased expression of numerous immediate early genes, including the gene encoding the transcription regulatory protein Myc. Myc increases the expression of many delayed-response genes, including some that lead to increased G₁-Cdk activity (cyclin D-Cdk4), which triggers the phosphorylation of members of the Rb family. This inactivates the Rb proteins, freeing gene regulatory protein E2F to activate the transcription of G₁/S genes including the including G₁/S cyclin (Cyclin E) and S-cyclin (Cyclin A). Cyclin E has a positive feedback on phosporylation of Rb thus pushing the cell cycle forward.

Question 40

What are Mitogens

Answer 40

• Extracellular signal molecules that stimulate cell division, primarily by triggering a wave of G₁/S-Cdk activity that relieves intracellular negative controls that otherwise block progress through the cell cyle
  *

Question 41

Question 42

Cell fate decisions are made at the

Answer 42

• Restriction point
  
  • Extracellular signals target cell cycle machinery controlling the Restriction point to make appropriate cell fate decisions

Question 43

Growth factors initiate positive feedback loop of

Answer 43

G1 cell cycle machinery driving Restriction point progression and growth factor independence

Question 44

Disrupted Restriction point control compromises cell fate decisions. Give examples

Answer 44

Obesity and B-cell loss in type II diabetes

Question 45

Question 46

Question 47

What are the three major Checkpoints in the cell cycle

Answer 47

Question 48

DNA Damage response

Answer 48

Question 49

What is p53

Answer 49

• The guardian of the genome
• Tumor suppressor protein regulating transcription to prevent genome corruption

Question 50

Answer 50

Question 51

Mechanism of Progeria (Hutchinson-Gilford Progeria Syndrome)

Answer 51

• Lamin A mutation prevents farnesyl group removal
• Lamin remains attached to nuclear rim and cannot form nuclear lamina to support nuclear envelope
• Prevents chromatin organization during mitosis, so cell division inhibited

Question 52

Mechanism of Ataxia Telangiectasia (ATM)

Answer 52

• Serine/threonine protein kinase recruited and activated by DNA damage (esp. Double-strand breaks)
• Phosphorylates key proteins activating DNA damage checkpoint
• Leads to cell cycle arrest, DNA repair or apoptosis