Dr. White-Genes (when things go right and wrong)

Question 1

What is signal transduction?

Answer 1

cell to cell communication

Question 2

what happens if the lectin gene is knocked out? (mice used as example) What is this an example of?

Answer 2

if leptin is knocked out, the mouse will not think that it is full and will continue eating, resulting in a fat mouse. This is an example of signal transduction.

Question 3

Describe endocrine signaling

Answer 3

long distance signaling, signal goes from bloodstream to distant target cells.
Freely diffusible signal and long lasting

Question 4

Describe paracrine signaling

Answer 4

acts locally and affects nearby cells (not as freely diffusible)
short lived signal

Question 5

Describe synaptic signaling

Answer 5

acts locally and affects cells nearby (not as freely diffusible)
short lived signal
ex: neurotransmitters

Question 6

Describe autocrine signaling

Answer 6

• cells respond to signals that they themselves release to cells of the same type
• cell secretes signal that feeds back and binds to a receptor on its own surface
  ex: growth factor in cancer cells

Question 7

Describe direct cell signaling

Answer 7

Ag-presenting cells to T cells

ex: immune cells

Question 8

What does the extracellular domain of the G protein coupled receptor do?

Answer 8

binds to ligand

Question 9

What does the transmembrane domain of the G protein coupled receptor do?

Answer 9

anchors receptor

Question 10

What does the cytoplasmic domain of the G protein coupled receptor do?

Answer 10

associates with G protein

Question 11

G proteins are ______ proteins composed of how many subunits?

Answer 11

heterotrimeric, 3 subunits: alpha, beta, gamma

Question 12

What do the heterotrimeric G proteins do?

Answer 12

regulate target enzymes

Question 13

REVIEW THE PATHWAY OF G PROTEIN SIGNALING

Answer 13

slide 13 of lecture

Question 14

What does adenylyl cyclase do?

Answer 14

generates cAMP which then goes on to interact with it’’s target protein to cause a biological response

Question 15

What occurs in cholera?

Answer 15

Cholera toxin modifies G protein by keeping the G alpha protein in the GTP active form indefinitely, making the pathway always active. Cl- and water pump out of cell in intestine, causing severe diarrhea.

Question 16

cAMP interacts with target proteins to cause what?

Answer 16

a biological response

Question 17

cAMP activate ______ which has ____ subunits

Answer 17

cAMP dependent protein kinase (PKA), 4 subunits

Question 18

When 2 cAMP molecules bind to the regulatory subunits of PKA what happens?

Answer 18

release of active C subunits

Question 19

Describe receptor tyrosine kinases (RTKs)

Answer 19

play important role in signal transduction
enzyme linked receptor
used for response to growth factors

Question 20

What are the components of RTKs?

Answer 20

extracellular domain
transmembrane domain
cytoplasmic domain which transmits signal through tyrosine kinase domain and adds phosphates to tyrosine on proteins

Question 21

review signaling by protein phosphorylation

Answer 21

slide 21

Question 22

What happens when a ligand binds to the RTK?

Answer 22

causes conformational change which induces dimerization of two receptor monomers and autophosphorylation occurs

Question 23

Autophosphorlyation of the the RTK causes what?

Answer 23

the receptor to act as a scaffold or docking sites to recruit other proteins to the plasma membrane, outside event (binding to receptor) gets transacted to a response inside the cell

Question 24

review RTK cascade

Answer 24

slides 24-27

Question 25

review JAK-STAT process

Answer 25

slide 28

Question 26

review serine-threonine receptor and smad

Answer 26

slides 29-30

Question 27

when signal is not turned off, Ras is constitutively activated from a point mutation of Gly to ____ and results in what?

Answer 27

Val, resulting in mutation (frequently found in human cancer)

Question 28

What makes cells different?

Answer 28

differences in gene expression

Question 29

describe the helix turn helix DNA-binding domain structural motif

Answer 29

- simplest - two alpha helices connected by short chain of amino acids that make turn at fixed angle - longer helix portion= recognition module-DNA binding module - binds DNA as dimers

Question 30

describe the zinc finger domain

Answer 30

- DNA binding motif includes Zn atom | - binds to major groove of DNA

Question 31

Describe the leucine zipper motif

Answer 31

- two alpha helical DNA binding domain - dimerizes through leucine zipper region - interactions between hydrophobic amino acid side chains (Leu) at every 7 aa down one side of alpha helix to form zipper structure - grabs DNA like clothespin

Question 32

describe the helix loop helix domain

Answer 32

- consists of a short alpha chain connected by a loop to a second longer alpha chain - can occur as homodimers or heterodimers - three domains: DNA binding domain, dimerization domain, activation domain

Question 33

describe regulation by RNA stability

Answer 33

- decapping: exposed mRNA degraded from 5' end (5' end serves to protect RNA from RNA degrading enzymes) - mRNA degraded from 3' end through poly-A tail and into coding region

Question 34

Why must post translational medications occur? and what occurs?

Answer 34

so the protein can be functional proteins fold into 3D conformations with the help of molecular chaperones co-factors bind

Question 35

What is the proteasome?

Answer 35

apparatus that deliberately destroys aberrant proteins?

Question 36

What is the specificity of the proteasome?

Answer 36

one E1 ubiquitin activating enzyme and 1 proteasome but 30 E2 ubiquitin conjugating enzymes and hundreds of E3 accessory proteins

Question 37

What is methylation and genomic imprinting?

Answer 37

what genes get expressed or not from mom and dad

Question 38

What is x-chromosome inactivation?

Answer 38

even things out- XX vs XY (2 X chromosomes vs one)

Question 39

What are the three major checkpoints of the cell cycle?

Answer 39

start: G1 to S G2 to M in M phase: anaphase and cytokinesis

Question 40

Describe the first checkpoint of the cell cycle

Answer 40

start-cell commits to cell cycle entry and chromosome duplication

Question 41

Describe the second checkpoint of cell cycle

Answer 41

G2/M: move into chromosome alignment on spindle in metaphase

Question 42

Describe the third checkpoint of cell cycle

Answer 42

metaphase to anaphase transition: triggers sister chromatin separation and cytokinesis

Question 43

What are Cdks?

Answer 43

heart of cell cycle control system--activities of Cdks rise and fall during cell cycle

Question 44

What proteins regulate Cdks?

Answer 44

cyclins

Question 45

Cyclin ____ vary according to point of time in cell cycle

Answer 45

levels

Question 46

When cyclin is not bound to Cdk, the active site is blocked by what?

Answer 46

region of protein called the T loop

Question 47

Phosphorylation of Cdk is cased by ____

Answer 47

CAK (Cdk activating enzyme)

Question 48

What does Wee1 and Cdc25 do to Cdk-Cyclin activities?

Answer 48

Wee1 kinase adds an inhibitory phosphate | Cdc25 phosphatase removes phosphate to activate Cdk

Question 49

What does CKI (Cdk inhibitory protein do)?

Answer 49

targets G1/S-Cdk and S-Cdks (slide 48)

Question 50

What are the targets in APC/C?

Answer 50

S-cyclin, M cyclin (slide 48)

Question 51

What does condensin do?

Answer 51

makes sister chromatids into short structures that can be pulled apart at anaphase with no breakage in 2 steps: chromosome condensation (dramatic compaction) and resolution (sister chromatids become distinct separate units)

Question 52

What is apoptosis?

Answer 52

programmed cell death

Question 53

What is the precursor of caspases?

Answer 53

procaspases

Question 54

What are the two major classes of caspases?

Answer 54

initiator and executioner caspases

Question 55

What do executioner caspases do?

Answer 55

destroys actual targets--executes apoptosis

Question 56

REVIEW APOPTOSIS SLIDES

Answer 56

slides 53-58

Question 57

What are oncogenes?

Answer 57

gain of function, "gas pedal", involves single mutation event and activation of gene causing proliferation

Question 58

What are tumor suppressor genes?

Answer 58

lose of function, "brake pedal", involve genes that inhibit growth. Mutation event: one gene- no effect, second mutation causes problems

Question 59

What are the ways oncogenes can be activated?

Answer 59

- deletion or point mutation in coding sequence - regulatory mutation - gene amplification - chromosome rearrangment

Question 60

What are the two major categories of tumor suppressor genes?

Answer 60

1. proteins that normally restrict cell growth and proliferation 2. proteins that maintain integrity of the genome

Question 61

What are the two forms of retinoblastoma (Rb)?

Answer 61

hereditary and sporadic | 40% of retinoblastoma is hereditary, 60% is sporadic

Question 62

describe the hereditary form of Rb

Answer 62

loss of function or deletion of one copy of Rb in every cell due to inherited defect, but have one good copy of Rb gene somatic event occurs: eliminates one good gene, cancer occurs loss of heterozygosity

Question 63

describe the sporadic form of Rb

Answer 63

non-cancerous cells fine- no mutation of Rb | two hit hypothesis: first Rb gene obtains mutation then need second mutation Rb

Question 64

What is a polyp?

Answer 64

precursor of colorectal cancer