Cell Cycle: Start/Restriction Point & S Phase Flashcards

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1
Q

The presence of each cyclin rises and falls at distinct points of the cell cycle. True or false?

A

True

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2
Q

Which cyclin is highest during S phase?

A

S-cyclin (Cyclin A)

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3
Q

Which cyclin is highest during G1?

A

G1/S-cyclin (cyclin E)

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4
Q

Which cyclin is highest during M phase?

A

M-cyclin (cyclin B) and decreasing S-cyclin (cyclin A)

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5
Q

Which cyclin is highest during G2?

A

S-cyclin (cyclin A) with M-cycling (cyclin B) rising

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6
Q

Familiarize yourself with this figure.

A
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7
Q

There are ___ classes of cyclins, each of which binds and activates specific ______..

A

Four

Cyclin-dependent kinases (Cdks)

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8
Q

There are four classes of cyclins: ____, ______, ______, and _____.

A

G1

G1/S

S

M

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9
Q

The cyclin and cyclin-dependent kinase complex G1-CDK in yeast is composed of ___________ and _________.

A

Cyclin 3 (Cln3)

Cyclin-dependent kinase 1 (CDK1)

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10
Q

The G1-CDK complex in mammals is composed of ____________ and _______________.

A

Cyclin D

Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6)

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11
Q

The G1/S-CDK complex for yeast is composed of ________ and/or ___________ and ____________.

A

Cyclin 1 and cyclin 2 (Cln1, Cln2)

CDK1

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12
Q

The G1/S-CDK complex in mammals is composed of ________ and _____________.

A

Cyclin E

CDK2

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13
Q

The G1-Cdk complex in vertebrates is composed of cyclin ___ and cyclin-dependent kinases ____ and ____. In yeast, this same complex is composed of cyclin (Cln) _____ and cyclin-dependent kinase _____.

A

Cyclin D

Cdk4 &Cdk6

Cln3

Cdk1

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14
Q

The G1/S-Cdk complex in verebrates is composed of cyclin ____ and cyclin-dependent kinase _____ while in yeast it is composed of cylcin (Cln) _____ and cyclin-dependent kinase ____.

A

Cyclin E

Cdk2

Cln1, 2

Cdk1

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15
Q

In yeast, G1 cyclin synthesis is stimulated by _________________ and ________________.

A

Nutrient accumulation and availability

Cell growth (i.e., size)

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16
Q

In mammalian cells, G1 cyclin synthesis is stimulated by __________, ________________, and ___________.

A

Nutrient accumulation and availability

Cellular growth (size)

Growth factor stimulation

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17
Q

The S-Cdk complex is composed of cyclin _____ and Cdk ____ and ____ in vertebrates and cyclin (Clb) ______ and Cdk1 in yeast.

A

Cyclin A

Cdk2 & Cdk1

Clb5, 6

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18
Q

Complete the table.

A

G1-Cdk, Cdk 4 & Cdk6

Cyclin A

Cdk1

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19
Q

Complete the table

A

G1-Cdk, Cdk4 & Cdk6

Cyclin E

Cyclin A, Cdk2 & Cdk1

M-Cdk, Cdk1

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20
Q

Complete the table.

A

G1-CDK, Cyclin D, Cdk4 & Cdk6, Cln3, Cdk1

Cyclin E, Cdk1

Cyclin A, Cdk2 & Cdk1, Cdk1

M-Cdk, Cdk1

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21
Q

Complete the table.

A

G1-Cdk, Cyclin D, Cdk4 & Cdk6, Cln3, Cdk1

G1/S-Cdk, Cyclin E, Cdk2, Cln1, 2, Cdk1

S-Cdk, Cyclin A,Cdk2 & Cdk1, Clb5, 6, Cdk1

M-Cdk, Cyclin B, Cdk1, Clb1, 2, 3, 4, Cdk1

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22
Q

In the M-Cdk complex, cyclin _____ and cdk _____ are present in vertebrates and cyclin ________ and cdk ____ in yeast.

A

Cyclin B

Cdk1

Clb 1, 2, 3, 4

Cdk1

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23
Q

The G1/S boundary is the “start” or _______________ point.

A

Restriction

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24
Q

What do cyclin dependent kinases do?

A

Regulate progression of the cell cycle at distinct stages

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25
Q

Cyclin-dependent kinases regulate progression at distinct stages of the _______ cycle.

A

Cell

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26
Q

Cyclin-dependent kinases can be regulated by _________ binding, ____________________, and ________________ binding.

A

Cyclin

Phosphorylation

CDK inhibitory proteins (CKIs)

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27
Q

What are three ways in which cyclin-dependent kinases (CDKs) are regulated?

A

(1) Binding of their respective cyclins,
(2) phosphorylation, which can activate or deactive them, and
(3) binding of CDK inhibitory proteins (CKIs)

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28
Q

What does CKI stand for?

A

Cyclin-dependent kinase (Cdk) inhibitory proteins

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29
Q

In yeast, G1 cyclin synthesis is stimulated by _________________ and ________________________.

A

Nutrient accumulation and availability

Cellular growth (increase in size)

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30
Q

In mammals, G1 cyclin (cyclin D) synthesis is stimulated by __________________, ____________________, and ________________.

A

Nutrient accumulation and availability

Cellular growth

Growth factor stimulation

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31
Q

What is the primary difference between yeast and mammalian cells regarding G1 cyclin synthesis?

A

Mammalian cells require growth factor stimulation

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32
Q

For all other cyclins, each active _______ initiaties a wave of ____________ activity, which produces a new _______.

A

Cdk

Transcriptional

Cyclin

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33
Q

How are cyclins degraded in the cell?

A

Ubiquitin-dependent proteolysis

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34
Q

What is required for ubiquitin-dependent proteolysis during the cell cycle?

A

Two E3 ubiquitin-ligases:

  1. SCF complex
  2. APC/C complex (anaphase promoting complex or cyclosome)
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35
Q

What does APC/C complex stand for?

A

Anaphase promoting complex or cyclosome

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36
Q

The SCF complex is active throughout the cell cycle but only recognizes _______________ targets.

A

Phosphorylated

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37
Q

What are two targets of the SCF complex?

A

G1 cyclins and CKIs (cyclin-dependent kinase inhibitors)

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38
Q

How does the SCF complex recognize its targets G1 cyclins and CKIs (cyclin-dependent kinase inhibitors)?

A

Phosphorylation

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39
Q

When is APC/C (anaphase promoting complex or cyclosome) active?

A

When phosphorylated by the M-cyclin/Cdk complex at the metaphase/anaphase transition

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40
Q

What phosphorylates APC/C (anaphase promoting complex or cyclosome)?

A

The M-cyclin/Cdk complex (cyclin B/Cdk1)

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41
Q

What does APC/C target?

A

Proteins that possess destruction box motifs (recognition sites for APC/C)

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42
Q

What proteins have destruction boxes?

A

S-cyclin (cyclin A), M-cyclin (cyclin B), and proteins that connect sister chromatids

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43
Q

What are the three targets of APC/C?

A
  1. S-cyclin (cyclin A)
  2. M-cyclin (cyclin B)
  3. Proteins that connect sister chromatids
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44
Q

In the absence of phosphorylation, ____________________________ (Cdks) still have activity but are much lower.

A

Cyclin-dependent kinases

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45
Q

Cyclin-dependent kinases (Cdks) are more active when ___________________.

A

Phosphorylated

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46
Q

CDKs are phosphorylated by ____________.

A

CDK activating kinases (CAKs)

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47
Q

CAKs (CDK activating kinases) are active throughout the cell cycle and _________________ the amino acid ____________ at the active site.

A

Phosphorylate

Threonine

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48
Q

Phosphorylation of the amino acid threonine by CAKs (CDK activating kinases) at the active site of CDKs increases their activity but is not the ______________ step.

A

Rate-limiting

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49
Q

What kinase phosphorylate and inhibit mitotic CDKs?

A

Wee1 kinases

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50
Q

What do Wee1 kinases phosphorylate on CDKs?

A

Tyrosine and threonine residues in the ATP binding site of CDK

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51
Q

Wee1 kinases phosphorylate a tyrosine and threonine residue in the _______________ site of CDK, which potently inhibits CDK activity.

A

ATP-binding site

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52
Q

How are phosphorylations completed by Wee1 kinases removed?

A

Cdc25 phosphatases

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53
Q

________ phosphatases dephosphorylate and therefore ___________ mitotic CDKs inhibitied by Wee1 kinase phosphorylation.

A

Cdc25

Activate

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54
Q

How many classes of CKIs are present in mammalian cells?

A

4

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55
Q

What does CKI stand for?

A

CDK inhibitors

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56
Q

What are the four classes of CKIs (CDK inhibitors) in mammalian cells?

A
  1. Wee1 kinases
  2. INK4 (G1 CDK inhibitors)
  3. p21CIP (G1/S and S CDK inhibitors)
  4. p27<strong>KIP1</strong> (G1/S and S CDK inhibitors)
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57
Q

What does INK4 stand for?

A

Inhibitors of kinase 4

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58
Q

What inhibits G1 CDKs (CDKs 4 & 6)?

A

INK4 (inhibitors of kinase 4)

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59
Q

How does INK4 (inhibitors of kinase 4) (a CKI) inhibit CDK4 and CDK6 in the G1 phase?

A

INK4 binds them, preventing cyclin binding

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60
Q

When is INK4 most likely to be expressed?

A

In response to excessive growth stimulation because it inhibits CDKs 4 & 6 from binding cyclin D

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61
Q

What does the “p” stand for in p21CIP and p27KIP1?

A

Protein

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62
Q

What are the G1/S (CDK2) and S (CDK2 & 1) CDK inhibitors (CKIs)?

A

p21CIP and p27KIP1

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63
Q

How do p21CIP and p27KIP1 act as CKIs (CDK inhibitors)?

A

Binding G1/S and S cyclin/CDK complexes, inhibiting CDK activity

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64
Q

As the activity of a particular CDK begins to increase, one of its targets is the ___________ that is trying to inhibit it.

A

CKI (CDK inhibitor)

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65
Q

How do CDKs inactivate CKIs?

A

CDKs bind CKIs when CDK levels increase, and CDK binding to CKIs inhibits CKIs

66
Q

What happens after a cyclin-dependent kinase (CDK) binds its CDK inhibitory protein (CKI) target?

A

SCF complex recognizes it via its substrate recognition partner, an F-box protein, and ubiquinates it

67
Q

How does a CDK inhibitor (CKI) become degraded?

A

Binding by CDK, ubiquinated by SCF complex via help of its substrate recgonition partner, an F-box protein

68
Q

What helps the SCF complex recognize CKIs (CDK inhibitors)?

A

A substrate recognition partner, an F-box protein

69
Q

What is an F-box protein?

A

A substrate recognition partner for the SCF complex

70
Q

How do cells commit to moving through the cell cycle?

A

Moving past the G1/S boundary

71
Q

What is the rate-limiting step for the cell cycle?

A

The G1/S boundary

72
Q

In yeast, the G1/S boundary is known as the “start” point whereas it is known as the “________________” point in mammalian cells.

A

Restriction point

73
Q

What do we mean by a “start” or “restriction point” in the cell cycle?

A

The cell is committed to moving through the cycle unless some significant problem occurs

74
Q

What is required for start in yeast?

A
  1. Sufficient nutrients and growth
  2. Sufficient level of Cln3 (cyclin 3), the G1 cyclin
  3. Synthesis of Cln1 and Cln2 (cyclin 1, cyclin 2), the G1/S cyclins
75
Q

What three things are required for start in yeast?

A
  1. Synthesis of Cln1 & 2
  2. Synthesis of enough Cln3 (G1 cyclin)
  3. Nutrient availability and appropriate cell size
76
Q

Cln3/CDK1 phosphorylate the transcriptional co-repressor of Cln1 and Cln2, ________, thereby enabling transcription of Cln 1 & 2 required for start.

A

Whi5

77
Q

What does Whi5 do?

A

It represses transcription of Cln 1 & Cln 2 and thereby regulates start

78
Q

What deactivates Whi5?

A

Phosphorylation by Cln3/CDK1, the G1 cyclin/CDK complex

79
Q

Regulation of Cln3 occurs at what level?

A

The level of translation

80
Q

The regulation of Cln 1 and Cln 2 occurs at what level?

A

The level of transcription

81
Q

How is Cln3 regulated?

A

When nutrients are scarce, translation of all proteins is inhibited, and nutrient available is detected and relayed through the Target of Rapamycin (TOR) kinase

82
Q

What is TOR kinase stand for?

A

Target of Rapamycin kinase

83
Q

What does TOR kinase do?

A

Target of Rapamycin kinase detects nutrient levels in yeast cells, ultimately regulating whether the cell will translate Cln3

84
Q

In mammalian cells, passing the _______________ point requires both growth factor signaling and sufficient nutrients.

A

Restriction

85
Q

Nutrient availability and binding by growth factors are relayed through a kinase called _____________________ in mammalian cells.

A

Mammalian Target of Rapamycin (mTOR)

86
Q

Which specific mTOR is involved in identifying nutrient availability and growth factoring binding?

A

mTOR complex 1 (mTORc1)

87
Q

Active mTOR phosphorylates three key substrates. What are they?

A
  1. S6 kinase
  2. 4E binding protein
  3. Transcription factors
88
Q

mTOR phosphorylates ______ and activates it, which then phosphorylates its target ___________.

A

S6 kinase

Ribosomal protein S6

89
Q

mTOR phosphorylates S6 kinase, which then phosphorylates ribosomal protein S6 because ribosomal protein S6 must be phosphorylated for the _______________ to engage translation.

A

Ribosome

90
Q

mTOR phosphorylates 4E binding protein, which normally binds eIF4E and ______________ eIF4E.

A

Inhibits

91
Q

How does 4E binding protein inhibit eIF4E?

A

By binding and sequesting eIF4E

92
Q

When 4E binding protein is phosphorylated by _______, it releases _________, allowing it to bind other eIFs and the 5’ cap of mRNA.

A

mTOR

eIF4E

93
Q

mTOR phosphorylates other transcription factors, too, which increase the _________________ synthesis.

A

Ribosomal subunit

94
Q

What regulates mTOR?

A
  1. Low ATP levels and environmental stress inhibit mTOR
  2. High amino acid levels and growth factor stimulation activate mTOR
95
Q

What two things inhibit mTOR?

A
  1. Low ATP levels, specifically ATP/AMP rato
  2. Environmental stress, like osmotic stress, oxidative stress, and high temperatures
96
Q

_____ ATP levels, and specifically low ATP:AMP ratios, ___________ mTOR as do ______________ stressors.

A

Low

Inhibit

Environmental

97
Q

What two things stimulate mTOR?

A
  1. High amino acids levels, especially leucine
  2. Growth factor stimulation
98
Q

What amino acid is especially significant in activating mTOR?

A

Leucine

99
Q

What G-protein activates mTOR?

A

Rheb

100
Q

What protein acts as the GAP (GTPase activating protein) for Rheb, which functions as the G-protein for mTOR?

A

Tuberous sclerosis 1/2 (TSC1/TSC2)

101
Q

What do TSC1/TSC2 stand for?

A

Tuberous sclerosis 1/2

102
Q

When TSC1/TSC2 is active, it binds and activates the G-protein _____, stimulating the hydrolysis of GTP to GDP. This _______ the G-protein and thereby decreases its ability to activate ______. Thus, for cell growth to occur, we want TSC1/TSC2 to be __________.

A

Rheb

Deactivates

mTORc1

Inactive

103
Q

What do tuberous sclerosis 1/2 (TSC1/TSC2) do regaring mTOR activation?

A

TSC1/TSC2 act as the GAP for Rheb, which is the G-protein that activates mTOR

104
Q

What phosphorylates and inactivates TSC2 of the TSC1/2 complex?

A

Protein kinase B (PKB)

105
Q

Under favorable conditions, Akt/PKB is activated. PKB then phosphorylates and _________ TSC2 of the _________ complex. Phosphorylation likely leads to the ___________ of the complex. As such, the complex can no longer function as the ______ for Rheb, so Rheb remains in its _____-bound state and active, thereby activating mTORc1 and increasing _________.

A

Inactivates

TSC1/TSC2

Dissociation

GAP (GTP-ase activating protein)

GTP-bound

Cell growth

106
Q

Under unfavorable conditions, specifically low ATP/AMP ratios, AMP kinase is activated, which in turn phosphorylates and activates _______, which increaseTSC1/2 complex levels. This allows for Rheb to hydrolyze its GTP for ____, thereby inhibiting its ability to activate _______.

A

TSC2

GDP

mTORc1

107
Q

______ ATP/AMP ratios activate ______, which in turn phosphorylates and activates TSC2, which causes the association of the TSC1/2 complex. The TSC1/2 complex can now act as the GAP for ____, thereby hydrolyzing its GTP for GDP. This causes its deactivation and decreases mTOR activity.

A

Low

AMP kinase

Rheb

108
Q

Which pathway mediates mTOR activation via growth factors?

A

PI3K via G-protein Rheb and its GAP TSC1/TSC2

109
Q

Which pathway mediates mTORc1 activation via amino acid levels?

A

The Rag complex of G-proteins

110
Q

When amino acid levels are high, mTORc1 is activated by ___________ G-proteins.

A

Rag complex

111
Q

Which pair of the Rag complex is GTP bound under high amino acid levels?

A

A&B

112
Q

Which pair of the Rag complex is GDP bound under high amino acid levels?

A

C&D

113
Q

What acts as the GEF (guanine nucleotide exchange factor) for RagA&B?

A

Ragulator

114
Q

Under low amino acid conditions, RagA&B are bound to ______________.

A

GDP

115
Q

Under low amino acid conditions, RagC&D are bound to ____________.

A

GTP

116
Q

What acts as the GAP (GTP-ase activating protein) for RagD?

A

Leucyl-tRNA synthetase

117
Q

When can leucyl-tRNA synthetase act as the GAP for Rag D?

A

Upon leucine binding

118
Q

Be able to describe the pathway that leads to mTORc1 activation via growth factor binding.

A
119
Q

In the presence of amino acids, mTORc1 is activated by what pathway?

A

The Rag complex

120
Q

How is mTORc1 activated by the Rag complex of G-proteins? In other words, what must be present in the cell for the pathway’s activation?

A

Amino acids, especially leucine

121
Q

How is mTORc1 activation different from other G-proteins we’ve encountered throughout the semester?

A

RagA/B must be GTP bound

Rag C/D must be GDP bound

122
Q

mTORc1 is activated by the ____________ complex of G-proteins. Amino acids activate ______________, the GEF for RagA/B, and leucine binds and activates _________________, the GAP for RagC/D. This allows for RagA/B to become ____-bound and RagC/D to become ____-bound, which is required for mTORc1 activation.

A

Rag complex

Ragulator

leucyl tRNA synthetase

GTP-bound

GDP-bound

123
Q

mTORc1 can be regulated by ATP levels when _____ kinase phosphorylates and activates TSC2.

A

AMP kinase

124
Q

ATP levels can also regulate mTORc1 by __________.

A

Inhibition

125
Q

____ATP:AMP ratios activate AMP kinase to either phosphorylate and activate ________, thereby inhibiting mTORc1, or directly phosphorylate and inhibit _______ because ____ levels signal to the cell that there is not enough energy for cell growth.

A

Low

TSC2

mTORc1

Low

126
Q

There are four cyclin/CDK pairs in ___________, two in ___________ yeast, and three in budding yeast.

A

Mammals

Fission yeast

127
Q

Be able to explain the major differences between cyclin/CDK complexes in fission yeast cells and mammalian cells.

A
128
Q

The order of cyclin/CDK complexes from G1 to M phase in mammalian cells: D, E, A, B; 4&6, 2, 2, 1.

A

Cyclin D/CDK4&6

Cyclin E/CDK2

Cyclin A/CDK2

Cyclin B/CDK1

129
Q

Growth factor binding its receptors activates the MAPK pathway. This results in transcription and translation of the G1 cyclin/CDK complex: _________. The G1 cyclin/CDK complex phosphorylates ______, which releases E2F, a ______________ that upregulates expression of S cyclin/CDK complex: _____________.

A

Cyclin D/CDK 4&6

Rb (Retinoblastoma)

Transcription factor

Cyclin E/CDK2

130
Q

_____ upregulates expression of cyclin E/CDK2, which then phosphorylates ____, releasing E2F and increasing its own expression.

A

E2F

Rb

131
Q

When enough cyclin __/CDK__ is accumulated in the yeast cell, the cell moves past the ____________ point or ______ boundary.

A

Cyclin 3/CDK2

start point

G1/S boundary

132
Q

At the beginning of G1 phase, Rb or _____________ binds and sequesters the transcription factor _______________.

A

Retinoblastoma

E2F

133
Q

What does Rb stand for?

A

Retinoblastoma

134
Q

What happens when cyclin D/CDK4&6 phosphorylate Rb?

A

Rb releases transcription factor E2F

E2F then upregulates transcription of cyclin E and CDK2

Cyclin E/CDK2 are required for transition from G1 phase to S phase

135
Q

What does Rb do in its unphosphorylated form?

A

Sequesters the transcription factor E2F

136
Q

In mammalian cells, cyclin ___/CDK4&6 promote progression from G1 to ____ phase while cyclin ___/CDK2 initiate ________ in late G1 phase. Cyclin ___/CDK2 initiate ________ in S phase, again, and cyclin B/CDK1 promotes mitosis in late ____ phase.

A

Cyclin D/CDK4&6

S phase

Cyclin E/CDK2

Replication

Cyclin A/CDK2

Replication

G2

137
Q

The transcription factor E2F, active G1/S cyclinE/CDK2 complex, and active S cyclinA/CDK2 complex all have a _______ feedback loop with E2F.

A

Positive

138
Q

E2F increases transcription of cyclin ____. Cyclin E/CDK2 in turn phosphorylate ____, which releases E2F.

A

Cyclin E

Rb

139
Q

Cyclin E/CDK2 or __________ phase complex increases the synthesis of the S-phase cyclin, cyclin ____.

A

G1/S phase

Cyclin A

140
Q

As protein synthesis increases, cyclin D and CDK4&6 levels increase; cyclin D/CDK4&6 phosphorylate ____ (retinoblastoma), which then releases the transcription factor E2F in the cytosol.

A

Rb

141
Q

The S phase is regulated in cells by regulating the S phase cyclin, which in yeast is ______ and in animals is ______. Initial S cyclin synthesis is stimulated by G1/S cyclin/CDK activity (i.e., cyclin E/CDK2). Upon its synthesis, the S chase cyclin is inhibited by _____ in yeast and _____ in animals. This keeps the cyclin inactivae until the correct time.

A

Clb5&6

Cyclin A

Sic1

p27<span>KIP</span>

142
Q

The G1/S cyclin/CDK complex ultimately overcomes the inhibition of the S phase cyclin via ____ in yeast and ____ in animals. The G1/S cyclin/CDK complex phosphorylates these CDK inhibitory proteins, leading to their ubiquination and degradation by the _____ complex.

A

Sic1

p27KIP1

SCF complex

143
Q

In yeast, Sic1 inhibits the S phase cyclin: _________. Once start occurs, the G1 cyclin/CDK complex (Cln3/CDK1) phosphorylates Sic1. This results in ubiquination and degradation of Sic1 by the SCF complex, which requires the help of _______ in identifying targets. Sic 1 must be phosphorylated ___ times in order for degradation to occur.

A

Clb5&6/CDK1

F-box protein

6 times

144
Q

How many times must Sic1 be phosphorylated in __________ yeast before it can be recognized by _______ and ubiquinated by SCF complex?

A

Budding

F-BOX protein

6 times

145
Q

Why must Sic1 be phosphorylated 6 times before it can be recognized by FBOX?

A

Poor affinity at some binding sites; requires high levels of G1/S cyclin/CDK (cyclin E/CDK2)

146
Q

What is the significance of Sic1 requiring phosphorylation 6 times?

A

Provides a sharp transition between G1 and S phases

147
Q

During _____ phase, replication of DNA occurs via multiple ________ of replication, but the pre-replication complex is assembled during _____ phase.

A

S phase

Origins of replication

G1

148
Q

What makes up the pre-recognition complex?

A

Origin recognition complex

Helicase

Loading factors, Cdc6 and Cdt1

149
Q

What three things are required for assembly of the pre-replication complex?

A
  1. Origin recognition complex
  2. Helicase
  3. Loading factors, Cdc6 and Cdt1
150
Q

Initiation of replication requires phosphorylation of the replication complex by two kinases: (1) _________, which phosphorylate initiator proteins that in turn recruit helicase activating factors and the DNA polymerase complex, and (2) __________, which phosphoryates MCM helicase.

A

CyclinA/CDK2

DDK

151
Q

When do the kinases that phosphorylate the replication complex become active?

A

S phase; they assembly during G1 and wait

152
Q

How does the cell ensure replication occurs only once?

A
  1. Loading factor Cdc6 is phosphorylated by cyclin A/CDK2 and targeted for ubiquination and degradation by SCF complex
  2. Loading factor Cdt detaches from pre-replication complex and bound by its inhibitor, geminin, which is later targeted by APC/C complex in M phase
  3. Helicase only loads when DNA is unphosphorylated; following replication, phosphorylated helicase is exported from the nucleus and only reenters the nucleus following dephosphorylation by phosphatases active during G1
153
Q

The loading factor ______ is phosphorylated by cyclin A/CDK2 and then targeted by ______ for degradation by the proteosome.

A

Cdc6

SCF complex

154
Q

After it helps the pre-replication complex attach, loading factor _____ is bound by its inhibitor ________, which is later targeted for degradation by the ________ complex in M phase.

A

Cdt1

Geminin

APC/C

155
Q

Helicase only loads onto DNA when it is phosphorylated or non-phosphorylated?

A

Non-phosphorylated

156
Q

What links sister chromatids together?

A

Cohesins

157
Q

Cohesins are made up of four subunits: two _____________ and two ___________.

A

Coiled-coils

Globulars

158
Q

Why are sufficient levels of Cln3 required in yeast for start to occur?

A

Cln3/CDK1 phosphorylate the transcriptional co-repressor Whi5, releasing its inhibition of Cln 1 and Cln2 transcription

159
Q

In yeast, Cln3/CDK1 complex phosphorylates the transcriptional co-repressor _______, which releases from DNA and allows for transcription of the next round of cyclins: _____ and _____.

A

Whi5

Cln1

Cln2

160
Q

For mTORc1 activation, RagA&B must be bound to _____ and RagC&D must be bound to ____.

A

GTP

GDP

161
Q

For activation of mTORc1, RagA&B must be in its GTP form. This requires that its GDP be exchanged for GTP by its GEF ______________. Simultaneously, RagC&D must be in its GDP form. This requires that its GTP be hydrolyzed to GTP by its GAP _______________.

A

Ragulator

Leucyl-tRNA synthetase

162
Q

For mTORc1 activation to occur under high amino acid conditions, __________ must bind leucyl-tRNA synthetase in the ___________ membrane. This activates the GAP function of leucyl-tRNA synthetase and results in RagC&D becoming _____ bound.

A

Leucine

Lysosomal

GDP-bound