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Cancer Biology > Cancer Bio - Exam 2 > Flashcards

Cancer Bio - Exam 2 Flashcards

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1
Q

Most signaling molecules are what?

A

Proteins

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2
Q

Proteins on the plasma membrane that bind to a specific ligand and transmit signal into the cells

A

Receptors

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3
Q

What two types of molecules can pass the plasma membrane?

A

Small and hydrophilic

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4
Q

Animal cells depend on ____ to divide (without, they can not).

A

Growth factors

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5
Q

Most cancer is induced in what type of pathway?

A

Cancer pathway

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6
Q

Why does signaling matter?

A

Error in signaling can lead to cancer formation

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7
Q

Not all ____ can cause cancer, only certain molecules related to cancer can cause cancer to form

A

Mutations

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8
Q

ErbB signaling network: How do cells communicate with their surroundings?

A

The ligands will bind to the receptors (growth factor receptors) in the plasma membrane.
Release adaptors and enzymes, causing signaling cascades in cytosol.
Causes transcription factors to bind.

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9
Q

5 stages of ErbB signaling network

A

Apoptosis (cell death)
Migration
Growth
Adhesion
Differentiation

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10
Q

Normal metazoan cells control what?

A

Each other’s lives

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11
Q

In order to creat normal tissue structure and function, the different cell types must what?

A

Coexist

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12
Q

The relative numbers and positions of each cell type must be what?

A

Tightly controlled

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13
Q

The cellular control is largely achieved via what?

A

The exchange of signals between cells within a cell type, and between different cell types.
(Can communicate between tissues)

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14
Q

Control is achieved by?

A

Exchange of signals between cells within a cell type and between different cell types

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15
Q

All the decisions made by an individual cell about its proliferation must represent what type of decision?

A

A consensus decision shared with cells that reside in the neighborhood.
Think: cell division, migration, death

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16
Q

Provide stem cells for renewal of the epithelium; stem cells that will become differentiated into epithelial cells.

A

Crypt

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17
Q

As cells divide, they more differentiated cells will move in which direction?

A

Upward; at the highest point, they will be well-differentiated, and they can survive up to a few days

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18
Q

All cell interaction is coordinated and occurs through what?

A

Through signal transduction

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19
Q

Src is what molecule?

A

A tyrosine kinase and acts as a signal transduction protein

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20
Q

What evidence proves that a single protein can affect many different behaviors/aspects of a cell?

A

Src affects other proteins and many different cellular functions. Src is can signal to affect other aspects of cell behavior and functions (i.e. division, etc.)

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21
Q

Technique used to detect proteins in the cell (ex. used to detect Src).

A

Western blot

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22
Q

Antibody in Src experiment was used against:

A

2-P-Y (phosphorylated tyrosine)

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23
Q

Once some proteins become phosphorylated, they can function as

A

signaling molecules

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24
Q

3 types of kinases:

A

Threonine (T), serine (S), tyrosine (Y)

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25
Q

What make up 99.9% of kinases?

A

Serine kinase and threonine kinase

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26
Q

Tyrosine kinases make up what portion of kinases?

A

<0.1%, but known to play critical role in cell division

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27
Q

When testing for Src-transformed NIH 3T3 cells and you run gel what would you expect to see?

A

Proteins will be separated by size (smaller = faster and larger = slower)

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28
Q

The first protein that the growth factor binds to

A

EGF-R (epidermal growth factor receptor)

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29
Q

All tyrosine kinase receptors (RTKs) consists of what three functional domains?
(hint: think of EGF-R domains)

A

Ectodomain (extracellular domain): 621 AA
Transmembrane domain: 23 AA
Cytoplasmic domain: 542 AA

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30
Q

Part of the cytoplasmic domain shows what with Src?

A

Homology

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31
Q

Once you add EGF-R, what happens to the cell?

A

Once growth factor is added, cells immediately start to divide (cells controlled by growth factor)

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32
Q

Can growth factors pass through the plasma membrane to control cell division?

A

No, but control cell division extracellullarly by binding immediately to the surface of the cell.

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33
Q

Growth factor binds to what domain?

A

The ectodomain

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34
Q

Domain that passes the plasma membrane

A

Transmembrane domain

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35
Q

What domain is the region of homology located?

A

Cytoplasmic domain (inside the cell - shows high homology for Src)

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36
Q

Since the growth factor receptor shows high homology to Src, we now know that the growth factor receptor is also a(n)

A

tyrosine kinase

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37
Q

3 features of tyrosine kinase receptors (RTKs):

A
  1. All tyrosine kinase receptors have the same 3 functional domains.
  2. The kinase (cytoplasmic?) domain is highly conserved.
    3.
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38
Q

Which proteins in the monkey kidney cells became phosphorylated?

A

Before growth factor addition, tyrosine phosphorylation levels were low. After, a lot of proteins became phosphorylated, especially proteins around plasma membrane.

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39
Q

Inhibitor of tyrosine kinase (inhibits phosphorylation)

A

AG1478

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40
Q

In absence of a growth factor, RTKs are

A

monomers (single peptides)

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41
Q

Since monomers can move freely on plasma membrane, they can bump into each other. In the presence of a growth factor, when RTKs bump into each other, the binding of the GF to the extracellular domain of the GF-R

A

Briefly increases affinity of the two receptors, causing dimerization; formation of a dimer (two peptides)

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42
Q

Two critical changes of RTKs following ligand binding (two important events of RTK activation):

A
  1. Dimerization
  2. Phosphorylation (transphosphorylation) of cytoplasmic domain
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43
Q

Two receptors aggregate together to form a complex

A

Dimer (dimerization)

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44
Q

Transphosphorylation

A

Kinase localized on one receptor, phosphorylate tails? on another receptor

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45
Q

Tumor virus that can cause tumor formation in birds

A

AEV (avian erythroblastosis virus)

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46
Q

AEV is similar to

A

RSV (rous-sarcoma virus)

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47
Q

Oncogene in AEV

A

v-EerbB

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48
Q

v-EerbB is similar to

A

Src
(think: AEV similar to RSV)

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49
Q

How can v-EerbB transform cells and cause cancer formation?

A

v-EerbB displays high homology to EGF-R; however, it lacks extra ectodomain (deletion)

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50
Q

The deletion of the ectodomain results in

A

conversion of the proto-oncogene into an oncogene

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51
Q

Need for ligand (i.e. growth factor) to bind to receptor for activation

A

Ligand-dependent firing

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52
Q

4 mechanisms to cause deregulation of receptor firing:

A
  1. deletion of ectodomain
  2. mutation (AA substitution)
  3. overexpression
  4. fusion of receptors
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53
Q

Dimerization and phosphorylation can become ligand-independent via receptor mutation, when

A

receptor is mutated (ex. deletion of extracellular receptor domain), the receptor behaves differently than normal

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54
Q

Dimerization and phosphorylation can become ligand-independent via mutation in any domain, by

A

substitution of amino acids

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55
Q

Dimerization and phosphorylation can become ligand-independent via overexpression, when

A

cell produces excessive amount of protein, so cell would contain numerous wild-type number of receptors, the cell would express excessive amount of the receptor, causing frequent collisions

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56
Q

Unrelated proteins covalently attack each other, forming

A

fusion protein

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57
Q

Fusion proteins can form

A

FIG proteins that can form a dimer (this is a problem because of abnormal activation)

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58
Q

Normal cells normally do not produce their own

A

ligands

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59
Q

3 major types of signaling:

A

Paracrine, autocrine, endocrine

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60
Q

signaling same cell; a form of signaling in which a cell manufactures its own mitogens

A

autocrine signaling

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61
Q

signaling long distance

A

endocrine signaling

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62
Q

signaling to neighboring cells

A

paracrine signaling

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63
Q

virus that affects cell division of mesenchymal cells (hint: it is a tumor virus)

A

Simian sarcoma virus

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64
Q

oncogene in Simian sarcoma virus

A

v-sis

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65
Q

T/F v-sis is similar to Src

A

true

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66
Q

cloning v-sis, showed its similarities to

A

PDGF

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67
Q

PDGF is a growth factor in

A

mesenchymal cells

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68
Q

A nuclear cell displays PDGF receptor, normal cell signaling division depends on (?) cells. When the cell is infected with Simian sarcoma virus, the cell will produce

A

v-sis protein ligand

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69
Q

v-sis protein ligand produced by infected cell can then bind to its own PDGF receptor, this is an example of

A

autocrine signaling (because cell produces its own “growth factor”, becoming autonomous)

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70
Q

autocrine signaling can lead to

A

deregulation of receptor firing

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71
Q

what number of proteins have general structures of the EGF-R and PDGF-R (in the human genome)

A

59

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72
Q

Deregulated activation caused by abnormal dimerization of RTKs (review):

A

Overexpression of receptors (dimerization via collision)
Mutation (AA substitution)
Deletion of ectodomain of RTKs
Fusion of RTKs to other proteins that dimerize

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73
Q

Ordered sequences of biochemical reactions inside the cell; with high specificity and speed

A

Signaling cascades

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74
Q

Light sensitivity/intensity unit of the eye (fruit fly); each is formed by a series of seven cells

A

Ommatidia

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75
Q

Gene that encodes a homolog of the FGF-R (a RTK) in ommatidium of fruit fly - so that it only contains 6 cells

A

Sevenless (homolog of RTK)

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76
Q

functions downstream of the sevenless and activates Ras

A

Sos (son of sevenless)

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77
Q

Sos in fly =

A

GEF (guanine nucleotide exchange factors; in yeast)

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78
Q

GEF affects

A

activity of guanine nucleotide binding protein (Ras)

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79
Q

Ras is a

A

signaling molecule that can switch between active/inactive; its activation state is determined by binding of guanine nucleotide

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80
Q

inactive form of Ras

A

binding GDP

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81
Q

active form of Ras

A

binding GTP

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82
Q

Sos can activate GEF, which converts the guanine nucleotide from

A

GDP to GTP (inactive to active Ras)

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83
Q

Molecule found in gap between sevenless and sos

A

Grb2

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84
Q

Signaling cascade upstream of Ras

A

RTK -> Grb2 -> Sos -> Ras

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85
Q

Signaling cascade upstream of Ras (for adaptive proteins)

A

RTK -> Shc -> Grb2 -> Sos -> Ras

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86
Q

Another molecule that can be found in gap between sevenless and sos (depending on type); adaptive proteins

A

Shc

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87
Q

RTKs affect physical location of downstream components without changing their intrinsic activity

A

Localization model

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88
Q

Two theoretical ways receptor can pass signal (activate) to downstream molecule

A
  1. activation (of surrounding molecules) - changing biochemical property of molecules, in presence of GF; phosphorylation – this was proved incorrect
  2. increase affinity of receptor by phosphorylation to attract molecules (in presence of GF); not changing biochemical property, but physical location – this is correct (localization model)
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89
Q

Src protein contains 3 domains:

A

SH1 (catalytic domain, (?) ATP)
SH2 (binding to pY-containing peptide)
SH3 (binding to proline-rich sequence domain)

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90
Q

A typical SH2 domain structure contains

A

100 amino acid residues

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91
Q

Structure of SH2

A

assembled from a pair of antiparallel beta-pleated sheets surrounded by alpha-helices

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92
Q

Sites on SH2 are responsible for what?

A

bind to phosphorylated tyrosine (pY); highly related to signaling transduction; can also bind to 3-6 amino acid (peptide) that follows pY

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93
Q

Function of SH2 domain

A

functions as modular plug, recognizing both pY and side-chains of AA (3-6) that flank the pY on its C-terminal side

94
Q

Human genome is estimated to encode at least ___ distinct SH2 groups.

A

120

95
Q

pY can attack proteins/substrates that contain
(proteins that are substrates of PDGF-beta-R (ex. src, GAP, SHP2, etc))

A

SH2

96
Q

the 3-6 amino acid residue determines what for pY

A

where it can bind on the proteins/substrates

97
Q

Why does one type of receptor (PDGF-R) recruit certain types of proteins and other receptors (EGF-R) recruits other types of proteins?

A

Each receptor contains unique residues (specificity)

98
Q

Grb2 and Shc are what kind of proteins

A

Bridging proteins

99
Q

Ras intrinsic activity; hydrolyzes GTP to GDP

A

GTPase

100
Q

GTPase-activating proteins

A

GAP

101
Q

3 effector molecules downstream of Ras

A

PI3K, Raf, Ral-GEF (each have different signaling pathways)

102
Q

Activated Ras attracts Raf from cytosol, the binding of Raf to Ras leads conformational changes of Raf;
Deregulation of this pathway contributes to certain cancer phenotypes (loss of contact inhibition, anchorage dependence, etc);
Deregulation can contribute to some cancers.

A

MAPK (mitogen-activated protein kinase) pathway

103
Q

Steps in MAPK pathway

A

Ras -> Raf -> MEK -> Erk 1 or 2 -> Mnk1 (and other proteins) -> elF4E (protein synthesis)

104
Q

cyclin D1; protein that drives cell proliferation

A

Ets

105
Q

Ras -> PI3K -> PIP3 -> Akt/PKB (or Rho-GEFs) -> Bad inhibition of apoptosis / mTOR stimulation of protein synthesis (cell growth) / GSK-3beta stimulation of cell proliferation

A

PI3 kinase pathway steps

106
Q

Functions to synthesize phosphatidylinositol (3,4,5) triphosphate (PIP3)

A

PI3K (phosphatidylinositol 3-kinase)

107
Q

A small minority of head groups in phospholipid bilayer contain ____ sugars

A

inositol

108
Q

Phospholipid structure + attach inositol sugar =

A

phosphatidylinositol (PI)

109
Q

3 components of PI (phosphatidylinositol):

A
  1. 2 fatty acids with long hydrocarbon tails
  2. glycerol
  3. phosphate and inositol
110
Q

PI kinases catalyzes the transition between

A

PI and PIP2
(phosphatidylinositol to phosphatidylinositol-4,5-diphosphate)

111
Q

PI3 kinases (PI3K) then leads PIP2 to become

A

PIP3 (phosphatidylinositol-3,4,5-triphosphate)

112
Q

PIP3 (binding site) attracts and activates which two molecules

A

Akt/PKB and Rho-GEF

113
Q

A pleckstrin homology (PH) domain-containing protein

A

Akt/PKB

114
Q

Functions of Akt/PKB:

A
  1. inhibit apoptosis
  2. stimulate cell division
  3. promote cell growth
115
Q

PIP3 formation/synthesis is controlled by which two proteins

A

PI3K and PTEN

116
Q

tumor suppressor protein in PIP3 formation/synthesis

A

PTEN

117
Q

PIP3 serves as docking site for

A

Akt/PKB (once they bind, Akt/PKB becomes phosphorylated and activated)

118
Q

T/F: Phospho-Akt promotes cell growth

A

True

119
Q

In mouse pten-/- epithelial cells (immunostained with antibody PTEN antibody), what happened to the cells?

A

Tumor cells grow because PTEN is lost

120
Q

In mouse pten cells immunostained with an anti-phospho-Akt/PKB-antibody, what happened to the cells?

A

There is abundance of PPI3

121
Q

Signaling pathways have what sort of relationship?

A

Interconnected

122
Q

T/F: Signaling pathways are linear

A

False

123
Q

Anti-growth genes

A

Tumor suppressor genes

124
Q

T/F: Oncogenes are more important than tumor suppressor genes.

A

False, just as important would be correct

125
Q

Prevalence of retinoblastoma

A

1 in 20,000 children (rare)

126
Q

Retinoblastoma age of diagnosis

A

birth to 6-8 years

127
Q

Two types of retinoblastoma:

A

unilateral and bilateral

128
Q

Affect only single eye

A

Unilateral retinoblastoma

129
Q

Affect both eyes

A

Bilateral retinoblastoma

130
Q

What form are unilateral retinoblastomas?

A

Sporadic form

131
Q

What form are bilateral retinoblastomas?

A

Familial form

132
Q

Rate of incidence with respect to time after retinoblastomas diagnosis:

A

36% bilateral at 50 years
5.69% unilateral at 50 years

133
Q

One hit and two hit theories were studied when

A

1971

134
Q

Bilateral retinoblastomas requires __#__ change(s)

A

1

135
Q

Each hit was presumed to represent what kind of mutation?

A

somatic

136
Q

In sporadic retinoblastoma, one somatic mutation leads to

A

one mutant Rb allele

137
Q

In familial retinoblastoma, one somatic mutation (one hit) leads to

A

two mutant Rb gene copies (tumor formation)

138
Q

In sporadic retinoblastoma, how many mutation events must occur to have two mutant Rb gene copies?

A

2 somatic mutations (two hit for tumor formation)

139
Q

Both Rb genes inactivated =

A

no functional genes (tumor formation)

140
Q

Occurence of a single mutation on a single gene

A

1 x 10^-6 per generation

141
Q

Occurence of a double mutation on a single gene

A

1 x 10^-12 per generation

142
Q

The first mutation is what kind of event

A

sporadic mutation

143
Q

The second mutation is what kind of event

A

loss of heterozygosity (LOH)

144
Q

Recombination occur during cell proliferation

A

Mitotic recombination

145
Q

Also called “allelic deletion”; a genetic alteration that converts a chromosome region from heterozygous to homozygous

A

Loss of heterozygosity (LOH)

146
Q

Which occurs more sporadic mutation or mitotic recombination?

A

Mitotic recombination occurs 10-100x more often than sporadic mutation

147
Q

Which occurs more loss of heterozygosity or mitotic recombination?

A

Loss of heterozygosity occurs more frequently than mitotic recombination

148
Q

Frequency of events (in order)

A

LOH > methylation > somatic mutation

149
Q
  1. DNA poly begins replication on template strand of red chromosome
  2. DNA poly jumps to template strand of homologous, green chromosome
  3. after copying segment of green template strand, DNA poly jumps back to template strand of red chromosome and continues copying
A

Gene conversion and LOH

150
Q
  1. Initial heterozygosity at Rb locus
  2. Nondisjunction at mitosis
  3. Subsequent loss of extra chromosome
A

Chromosomal nondisjunction and LOH

151
Q

What chromosome region is deleted in retinoblastoma patients?

A

Chromosome 13, 2nd and 4th bands of the 1st region on the long (q) arm of chromosome 13; 13q12-13q14

152
Q

What year were mutations of the Rb gene in retinoblastomas discovered?

A

1986

153
Q

The molecular governor of the R point transition in cell cycling

A

Rb

154
Q

Unphosphorylated Rb binds to the E2F, and this binding prevents E2F from…

A

activating the transcription of genes coding for proteins required for DNA replication in S phase

155
Q

In cells stimulated by growth factors, what phosphorylates the Rb protein?

A

activated CDK-cyclin

156
Q

Can phosphorylated or unphosphorylated Rb bind to E2F?

A

Phosphorylated Rb cannot. Unphosphorylated Rb can.

157
Q

Number of tumor suppressor genes:

A

> 50

158
Q

Important mechanism in shutting down tumor suppressor genes; covalently attach methyl group to a cytosine base; heritable, reversible

A

DNA methylation

159
Q

DNA methylation steps

A
  1. covalently attach methyl group to cytosine base
  2. in mammalian cells, methylation is found only when cytosines are located in a position that is 5’ to guanosines: MeCpG
  3. When MeCpG occurs in the vicinity of a gene promoter, expression of gene can be repressed
160
Q

Important mechanism in inactivating tumor suppressor genes in tumors

A

Promoter methylation

161
Q

The study of heritable changes in gene function that occur without a change in the DNA sequence

A

Epigenetics

162
Q

One copy is methylated, the second is lost through

A

LOH

163
Q

DNA methylation and LOH work together to

A

shut down suppressor genes

164
Q

Colonic polyps are common in what group of people

A

Very common in age 70+

165
Q

What percentage of colon cancer is sporadic?

A

> 95%

166
Q

Carpet of hundreds of small polyps in the colon; finger-like projections

A

Familial adenomatous polyposis (FAP)

167
Q

Contributes to cell proliferation; controls cancer formation (colon cancer and others) by controlling abundance of B-catenin protein

A

Wnt-B-catenin pathway

168
Q

tag phosphorylated B-catenin for degradation

A

Apc

169
Q

Why cells can’t divide in absence of Wnt

A

low B-catenin

170
Q

controls cells division; acts like growth factor
(in Wnt-B-catenin pathway)

A

Wnt

171
Q

In a normal cell, B-catenin is

A

synthesized then phosphorylated then degraded

172
Q

Phosphorylates B-catenin, so that Apc can identify and tag it for degradation

A

GSK-3B (glycogen synthase kinase-3B)

173
Q

When GSK-3B is inactive/enzymatically dead,

A

Apc can not tag B-catenin for degradation, so B-catenin accumulates and is in abundance

174
Q

Binding of Wnt to the frizzled receptors causes inhibition of

A

GSK-3B, preventing phosphorylation and degradation of B-catenin

175
Q

B-catenin associates with ____ in the nucleus and drives cell proliferation

A

TF Tcf/Lef

176
Q

B-catenin is similar to myc, playing a role in cell proliferation, except it is not a:

A

transcription factor

177
Q

Wnt is secreted by

A

stroma cells

178
Q

In mutated/deregulated colonic crypts, Apc protein is defective, B-catenin levels remain high in absence of intense Wnt signaling. Cells stop migrating upward, accumulate within crypts, and ultimately generate a

A

adenomatous polyp (colon polyp)

179
Q

Stem cells receive Wnt signal from stroma. B-catenin interacts with Tcf/Lef and promotes proliferation in stem cells. When cells move upward, stimulation by Wnts decreases, leading to increased degradation of B-catenin. Cells enter apoptosis after 3-4 days

A

normal cells (colon polyp)

180
Q

Apc structure

A

contains multiple protein binding domains, and the gene encoding Apc is frequently mutated

181
Q

mutations that affect B-catenin binding

A

germ-line mutations and somatic mutations (proving function of Apc)

182
Q

3 major suppressor types:

A
  1. PTN: convert PiP3
  2. PRB: control cell proliferation; control transcription
  3. Acp: target B-catenin for degradation
183
Q

2 types of anti-growth genes

A

gatekeepers and caretakers

184
Q

directly control biology of cells by affecting how they proliferate, differentiate, or die

A

gatekeepers

185
Q

control biology of cells through maintenance of cellular genomes

A

caretakers

186
Q

gatekeepers are

A

tumor suppressor genes

187
Q

a protein neckwork (signal processing circuit) that receives signals from various sources outside and inside the cells, integrates them, and decides the cell’s fate

A

cell cycle clock

188
Q

Where is the cell cycle clock located?

A

nucleus

189
Q

4 phases of mammalian cell cycle

A

M, G1, S, G2

190
Q

nuclear division and cytoplasm division; ~ 1 hr

A

mitotic phase

191
Q

G1 phase lasts approximately

A

12-15 hrs

192
Q

S (synthesis) phase lasts approximately

A

6-8 hrs

193
Q

G2 phase lasts approximately

A

3-5 hrs

194
Q

can’t see DNA under normal light microscope (need electron microscope)

A

interphase

195
Q

DNA visible under light microscope.
Mitotic spindle will assemble; centrosome moves in opposite direction

A

prophase

196
Q

Chromosome displayed central in dividing cell

A

metaphase

197
Q

Chromatids move in opposite direction

A

anaphase

198
Q

Chromatids reached the 2 poles.
Nuclear membrane becomes reformed (was fragmented)

A

telophase

199
Q

Interphase consists of

A

G1, S, G2

200
Q

Karyotype of normal cells, replicate how many times

A

once

201
Q

Karyotype of Rad17-deficient cells

A

malfunction/no function -> continue replicating

202
Q

point where cell makes decision to advance through remainder of cell cycle through M phase, to remain in G1, or retreat from active cell cycle to G0

A

restriction point

203
Q

before and at the restriction point, cell pays attention to

A

environment

204
Q

regulatory subunits of heterodimeric protein kinases that control cell cycle events

A

cyclin

205
Q

a group of serine/threonine kinases that are involved in regulation of cell cycle; push from one phase to another via phosphorylation; dependent on cyclin

A

CDKs

206
Q

cyclin-CDK complexes depend on

A

the association of a specific cyclin type having a physical interaction with CDK

207
Q

cyclin A + CDK increases catalytic activity of CDK2 by ____ fold

A

400,000

208
Q

types of cyclin

A

A, B, D, E

209
Q

3 types of CDK

A

CDC2, CDK4/6, CDK2

210
Q

cyclin B pairs with

A

CDC2 in M phase

211
Q

cyclin D pairs with

A

CDK4/6 in G1 phase to R point

212
Q

cyclin E pairs with

A

CDK2 from R point to S phase

213
Q

cyclin A pairs with

A

CDK2 for first 1/2 of S phase
CDC2 for second 1/2 of S phase and whole G2 phase

214
Q

cell cycle progression depends on changes in levels and availability of

A

cyclin during the various phases

215
Q

Fluctuation of cyclin B, E, and A levels during cell cycle in most mammalian cells

A

are tightly coordinated with schedule of advances through various phases

216
Q

Extracellular signals (especially mitogenic growth factors) strongly influence levels of cycle type

A

D (can sense/respond to environmental conditions)

217
Q

D-type cyclins serve to convey signals from extracellular environment to the

A

cell cycle clock in the cell nucleus

218
Q

there are various pathways involved in control of cyclin type ____ expression

A

D1

219
Q

What percentage of the cell cycle is influenced by extracellular signals and automatically programmed?

A

80-90% of G1 = extracellular signals
10-20% of G1, S, G2, M = automatic

220
Q

Cyclin-CDK complexes are regulated by ____; a group of proteins that affect activities of cyclin-CDK complexes

A

CDK inhibitors (CDKIs)

221
Q

Seven important CDKIs (tumor suppressor proteins)

A

4 INK4 (inhibitors of CDK4); affect only CDK4/6
3 other affect CDK2 and CDC2 (CDK4/6)

222
Q

TGF-B can inhibit cell division via

A

expression of p15^INK4B and weakly, p21^Cip1

223
Q

DNA damage causes rapid increases in

A

p21^Cip1

224
Q

blot technique to detect mRNA

A

northern blot

225
Q

molecular governor of R point transition

A

pRb

226
Q

highly phosphorylated Rb; happens around restriction point

A

hyperphosphorylation

227
Q

weakly phosphorylated

A

hypophosphorylation

228
Q

CDK4/6 converts

A

unphosphorylated to hypophosphorylated

229
Q

phase at which E2F is released

A

late G1, after hyperphosphorylation at R point, pRb releases E2Fs, allowing E2Fs to function as TFs

230
Q

pRb binds to E2Fs, blocking transcription activated domain

A

early/mid G1 when unphosphorylated/hypophosphorylated

231
Q

As cells enter into S phase the E2Fs are

A

inactivated and/or degraded

Cancer Biology (1 decks)

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