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

1
Q

What is signal transduction?

A

cell to cell communication

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2
Q

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

A

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.

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3
Q

Describe endocrine signaling

A

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

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4
Q

Describe paracrine signaling

A

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

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5
Q

Describe synaptic signaling

A

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

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6
Q

Describe autocrine signaling

A
  • 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
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7
Q

Describe direct cell signaling

A

Ag-presenting cells to T cells

ex: immune cells

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8
Q

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

A

binds to ligand

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9
Q

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

A

anchors receptor

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10
Q

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

A

associates with G protein

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11
Q

G proteins are ______ proteins composed of how many subunits?

A

heterotrimeric, 3 subunits: alpha, beta, gamma

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12
Q

What do the heterotrimeric G proteins do?

A

regulate target enzymes

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13
Q

REVIEW THE PATHWAY OF G PROTEIN SIGNALING

A

slide 13 of lecture

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14
Q

What does adenylyl cyclase do?

A

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

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15
Q

What occurs in cholera?

A

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.

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16
Q

cAMP interacts with target proteins to cause what?

A

a biological response

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17
Q

cAMP activate ______ which has ____ subunits

A

cAMP dependent protein kinase (PKA), 4 subunits

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18
Q

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

A

release of active C subunits

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19
Q

Describe receptor tyrosine kinases (RTKs)

A

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

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20
Q

What are the components of RTKs?

A

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

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21
Q

review signaling by protein phosphorylation

A

slide 21

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22
Q

What happens when a ligand binds to the RTK?

A

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

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23
Q

Autophosphorlyation of the the RTK causes what?

A

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

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24
Q

review RTK cascade

A

slides 24-27

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25
Q

review JAK-STAT process

A

slide 28

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26
Q

review serine-threonine receptor and smad

A

slides 29-30

27
Q

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

A

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

28
Q

What makes cells different?

A

differences in gene expression

29
Q

describe the helix turn helix DNA-binding domain structural motif

A
  • 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
30
Q

describe the zinc finger domain

A
  • DNA binding motif includes Zn atom

- binds to major groove of DNA

31
Q

Describe the leucine zipper motif

A
  • 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
32
Q

describe the helix loop helix domain

A
  • 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
33
Q

describe regulation by RNA stability

A
  • 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
34
Q

Why must post translational medications occur? and what occurs?

A

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

35
Q

What is the proteasome?

A

apparatus that deliberately destroys aberrant proteins?

36
Q

What is the specificity of the proteasome?

A

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

37
Q

What is methylation and genomic imprinting?

A

what genes get expressed or not from mom and dad

38
Q

What is x-chromosome inactivation?

A

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

39
Q

What are the three major checkpoints of the cell cycle?

A

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

40
Q

Describe the first checkpoint of the cell cycle

A

start-cell commits to cell cycle entry and chromosome duplication

41
Q

Describe the second checkpoint of cell cycle

A

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

42
Q

Describe the third checkpoint of cell cycle

A

metaphase to anaphase transition: triggers sister chromatin separation and cytokinesis

43
Q

What are Cdks?

A

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

44
Q

What proteins regulate Cdks?

A

cyclins

45
Q

Cyclin ____ vary according to point of time in cell cycle

A

levels

46
Q

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

A

region of protein called the T loop

47
Q

Phosphorylation of Cdk is cased by ____

A

CAK (Cdk activating enzyme)

48
Q

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

A

Wee1 kinase adds an inhibitory phosphate

Cdc25 phosphatase removes phosphate to activate Cdk

49
Q

What does CKI (Cdk inhibitory protein do)?

A

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

50
Q

What are the targets in APC/C?

A

S-cyclin, M cyclin (slide 48)

51
Q

What does condensin do?

A

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)

52
Q

What is apoptosis?

A

programmed cell death

53
Q

What is the precursor of caspases?

A

procaspases

54
Q

What are the two major classes of caspases?

A

initiator and executioner caspases

55
Q

What do executioner caspases do?

A

destroys actual targets–executes apoptosis

56
Q

REVIEW APOPTOSIS SLIDES

A

slides 53-58

57
Q

What are oncogenes?

A

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

58
Q

What are tumor suppressor genes?

A

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

59
Q

What are the ways oncogenes can be activated?

A
  • deletion or point mutation in coding sequence
  • regulatory mutation
  • gene amplification
  • chromosome rearrangment
60
Q

What are the two major categories of tumor suppressor genes?

A
  1. proteins that normally restrict cell growth and proliferation
  2. proteins that maintain integrity of the genome
61
Q

What are the two forms of retinoblastoma (Rb)?

A

hereditary and sporadic

40% of retinoblastoma is hereditary, 60% is sporadic

62
Q

describe the hereditary form of Rb

A

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

63
Q

describe the sporadic form of Rb

A

non-cancerous cells fine- no mutation of Rb

two hit hypothesis: first Rb gene obtains mutation then need second mutation Rb

64
Q

What is a polyp?

A

precursor of colorectal cancer