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Cell and Molecular Biology > Module 5: Cell Signaling: 4 Alternative Signaling Routes in Gene Regulation > Flashcards

Module 5: Cell Signaling: 4 Alternative Signaling Routes in Gene Regulation Flashcards

1
Q

What do extracellular signaling molecules often change to carry out their effects?

A

Gene expression

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2
Q

How do extracellular signaling molecules initiate changes in gene expression?

A

By initiating signaling pathways that change the activities of transcription regulators

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3
Q

What is a less common mechanism for controlling gene expression?

A

Pathways that depend on regulated proteolysis.

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4
Q

How can gene expression be controlled in relation to the daily cycle?

A

By the circadian rhythm

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5
Q

Name one mechanism that controls the activity and location of latent transcription regulators.*

A

Regulated proteolysis

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5
Q

The daily cycle of light and dark that influences gene expression.

A

circadian rhythm?

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6
Q

Control cell-fate choices, regulating pattern formation, and continual tissue renewal.

A

Notch receptor protein

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7
Q

In which process is the Notch receptor protein best known to play a role?

A

Production of Drosophila neural cells.

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8
Q

What happens when a precursor cell commits to becoming a neural cell in Drosophila?

A

It signals to its immediate neighbors **not to become neural cells.

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9
Q

What is the mechanism called where a neural precursor inhibits neighboring cells from becoming neural cells?

A

Lateral inhibition

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10
Q

What type of signaling mechanism does lateral inhibition depend on?

A

Contact-dependent signaling

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11
Q

What signal protein is involved in lateral inhibition where it binds to notch receptor protein?

A

Delta

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12
Q

What does Delta bind to during lateral inhibition?

A

Notch receptor protein

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13
Q

What happens when the Notch signaling process is defective?*

A

excess of neural cells is **produced **at the expense of epidermal cells, which can be lethal.

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14
Q

What happens to the neighboring cells that are inhibited during lateral inhibition?*

A

develop into epidermal cells

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15
Q

A single-pass transmembrane protein and latent transcription regulator.

A

Notch protein

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16
Q

What process is required for Notch to function?

A

Proteolytic processing

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17
Q

the breakdown of proteins into smaller polypeptides or amino acids*

A

proteolysis

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18
Q

What are the steps involved in the activation of Notch proteins? (5)

A
  1. Delta binds to Notch - Delta, a membrane-bound ligand, binds to the Notch receptor.
  2. Protease cleaves Notch - A plasma-membrane-bound protease cleaves the cytoplasmic tail of Notch.
  3. Cytoplasmic tail translocates to the nucleus - The cleaved tail moves into the nucleus.
  4. Activation of Notch response genes - The tail activates transcription of Notch response genes by binding to a DNA-binding protein.
  5. Conversion of repressor to activator - The tail transforms the DNA-binding protein from a transcriptional repressor into a transcriptional activator.
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19
Q

What triggers the activation of Notch?

A

Binding of Delta to Notch

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20
Q

Activation of Notch: What cleaves the cytoplasmic tail of Notch upon activation? Where does the cleaved Notch cytoplasmic tail translocate? (2)

A
  • Plasma-membrane-bound protease
  • Into the nucleus
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21
Q

Activation of Notch: What does the Notch cytoplasmic tail activate in the nucleus?

A

Transcription of Notch-response genes

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22
Q

Activation of Notch: How does the Notch cytoplasmic tail interact with DNA-binding proteins?

A

it binds to it

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23
Q

Activation of Notch: Notch converts DNA-binding proteins from transcriptional repressors into __.

A

transcriptional activators

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24
Q

How many proteolytic cleavage steps does the Notch receptor undergo? How many of the cleavage steps depend on Delta binding? (2)

A
  • 3
  • 2
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25
Q

What are the three steps involved in the proteolytic cleavage of Notch receptors? What is the final cleavage? (4)

A
  • 1st – normal biosynthesis
  • 2nd – binding of Delta to Notch
  • 3rd – cutting free the cytoplasmic tail of the activated receptor
  • final cleavage - mediated by γ-secretase to release the Notch tail.
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26
Q

Which cleavage step of the Notch receptor occurs during normal biosynthesis?

A

1st

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27
Q

Where does the first cleavage of Notch occur?*

A

golgi apparatus

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28
Q

What cleavage step of the Notch receptor occurs in the binding of Delta to the Notch receptor?

A

2nd

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29
Q

What mediates the second cleavage of Notch?*

A

extracellular protease

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30
Q

What cleavage step of the Notch receptor occurs when the cytoplasmic tail of the activated receptor releases a Notch?

A

3rd

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31
Q

What enzyme complex mediates the final cleavage of the Notch tail?

A

γ-secretase

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32
Q

What condition is associated with mutations in the gene encoding Presenilin (the essential subunit of γ-secretase involved in Notch cleavage)?*

A

Early-onset familial Alzheimer’s disease

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33
Q

Is Notch activation reversible?*

A

No

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34
Q

Secreted signal molecules that act as local mediators and morphogens.

A

Wnt proteins

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35
Q

In which organisms were Wnt proteins independently discovered? (2)

A
  • Drosophila (flies)
  • mice
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36
Q

In drosophila, it acts as a morphogen in wing development.

A

Wingless (Wg) gene

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37
Q

In mice, it promotes the development of breast tumors when activated by a viral integration.

A

Int1 gene

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38
Q

What are the two main signaling pathways activated by Wnt proteins? (2)

A
  • Wnt/β-catenin pathway
  • planar polarity pathway
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39
Q
  • A signaling pathway involving β-catenin as a latent transcription regulator.
  • involved in regulating the proteolysis of β-catenin
A

Wnt/β-catenin pathway

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40
Q

A signaling pathway that coordinates the polarization of cells in the plane of a developing epithelium.

A

planar polarity pathway

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41
Q

What happens to β-catenin in unstimulated cells?*

A

degraded rapidly

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42
Q

What stabilizes cytoplasmic β-catenin in cells?*

A

Wnt signaling

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43
Q

Wnt/β-catenin pathway: In cell-cell junctions, what contributes to the control of cell-cell adhesions?

A

β-catenin

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44
Q

In the Wnt/β-catenin pathway, it binds to β-catenin, keeps it out of the nucleus, and promotes its degradation.

A

degradation complex

45
Q

In the Wnt/β-catenin pathway, which two kinases are responsible for phosphorylating β-catenin? (2)

A
  • Casein kinase 1 (CK1)
  • glycogen synthase kinase 3 (GSK3)
46
Q

In the Wnt/β-catenin pathway, which hold the protein degradation complex together? (2)

A
  • axin
  • Adenomatous polyposis coli (APC)
47
Q

What are the two co-receptors that Wnt proteins interact with? (2)

A
  • Frizzled protein
  • LDL-receptor-related protein (LRP)
48
Q

In the Wnt/β-catenin pathway, what proteins are recruited upon activation of the Wnt receptor complex?

A

Dishevelled scaffold proteins

49
Q

In the Wnt/β-catenin pathway, which kinases promote the phosphorylation of the LRP receptor? (2)

A
  • Casein kinase 1 (CK1)
  • glycogen synthase kinase 3 (GSK3)
50
Q

In the Wnt/β-catenin pathway, what is brought to the receptor complex and inactivated, disrupting the β-catenin degradation complex?

A

Axin

51
Q

In the Wnt/β-catenin pathway, what happens to β-catenin when the degradation complex is disrupted? (2)

A
  • accumulates; and
  • translocates to the nucleus
52
Q

In the Wnt/β-catenin pathway, it alters the pattern of gene transcription.

A

β-catenin in the nucleus

53
Q

The composition of the inhibitory complex when there is no Wnt signaling is __ bound to a co-repressor protein of the __.

A
  • LEF1/TCF family proteins
  • Groucho family
54
Q

In the Wnt/β-catenin pathway, it acts as a coactivator, inducing the transcription of Wnt target genes.

A

β-catenin (when Wnt signaling is present)

55
Q

In the Wnt/β-catenin pathway, it causes a switch from transcriptional repression to transcriptional activation.

A

Wnt signaling

56
Q

Which important regulator of cell growth and proliferation is activated by β-catenin?

A

Myc

57
Q

What percentage of human colon cancers involve mutations in the Apc gene?

A

80%

58
Q

Mutations in the __ on __ inhibit β-catenin’s ability to bind to Apc, allowing β-catenin to __ in the __.

A
  • Apc gene
  • β-catenin
  • accumulate
  • nucleus
59
Q

When β-catenin accumulates in the nucleus, it stimulates the transcription of __ and other __.

A
  • c-Myc
  • Wnt target genes
60
Q

The wnt/β-catenin pathway contributes to cancer development due to uncontrolled cell growth and proliferation due to the activation of __, even in the absence of __.

A
  • target genes
  • Wnt signaling
61
Q

Secreted signal molecules that act as local mediators and morphogens.

A

hedgehog proteins

61
Q

Hedgehog proteins activate latent transcription regulators by inhibiting their __.

A

degradation

62
Q

Hedgehog signaling triggers a switch from transcriptional __ to transcriptional __.

A
  • repression
  • activation
63
Q

What can excessive hedgehog signaling in adult cells lead to?

A

Cancer

64
Q

In which organism was the first hedgehog protein discovered?

A

Drosophila

65
Q

When the __ is mutated in Drosophila, the larva is covered with __ processes (denticles), resembling a hedgehog.

A
  • Hedgehog gene
  • spiky
66
Q

What are the names of the genes encoding hedgehog proteins in vertebrates? (3)

A
  • Sonic
  • Desert
  • Indian hedgehog
67
Q

Hedgehog proteins mediate signaling through a latent transcription regulator called __(__).

A

Cubitus interruptus (Ci)

68
Q

Cubitus interruptus (Ci) in the absence of hedgehog signal is __ and proteolytically cleaved in __.

A
  • ubiquitylated
  • proteasomes
69
Q

Cubitus interruptus (Ci) is processed into __ that act as a transcriptional __, keeping hedgehog-responsive genes __, instead of __.

A
  • smaller fragments
  • repressor
  • silent
  • complete degredation
70
Q

Which kinases are involved in the processing of the cubitus interruptus (Ci) protein? (3)

A
  • PKA (protein kinase A)
  • GSK1
  • CK1
71
Q

The function of the complex formed by __ and __ proteins keeps unprocessed cubitus interruptus (Ci) out of the nucleus.

A
  • Fused
  • Costal2
72
Q

Hedgehog proteins __ the __ of cubitus interruptus (Ci), allowing it to function as a transcriptional __.

A
  • block
  • proteolytic processing
  • activator
73
Q

What are the names of the transmembrane proteins involved in hedgehog signaling? (3)

A
  • Patched
  • iHog
  • Smoothened
74
Q

In the absence of the hedgehog signal, __ keeps Smoothened sequestered and inactive.

A

Patched

75
Q

The binding of hedgehog to __ and Patched inhibits the activity of Patched and induces __ and __.

A
  • iHog
  • endocytosis
  • degradation
76
Q

Upon hedgehog binding, __ translocates to the plasma membrane and this recruits a protein complex containing (3)

A

Smoothened
- Ci
- Fused
- Coastal2

77
Q

When Costal2 is no longer able to bind the other three kinases, Ci is not cleaved and can now enter the __.

A

nucleus

78
Q

Costal is no longer able to bind the other 3 kinase, __ no longer cleaved and can now enter the __ and activate the transcription of __

A
  • Ci
  • nucleus
  • Hedgehog target genes
79
Q

The increase in Patched proteins serves as a __ feedback mechanism to inhibit further hedgehog signaling.

A

negative

80
Q
  • This pathway involves latent transcription regulators that play a crucial role in stress, inflammatory, and innate immune responses.
  • Overactivation of this pathway is often found in various human cancers.
A

NFκB-Dependent Signaling Pathway

81
Q

has important functions during normal animal development; for example, in Drosophila, the Dorsal protein is essential for specifying the dorsal-ventral axis of the developing embryo.

A

NFκB signaling

82
Q

NFκB signaling has important functions during normal animal development; for example, in Drosophila, the __ is essential for specifying the __of the developing __.

A
  • Dorsal protein
  • dorsal-ventral axis
  • embryo
83
Q

__ in Drosophila, __, in vertebrates, recognize pathogens and activate the NFκB pathway to trigger innate immune responses.

A
  • Toll receptors
  • Toll-like receptors
84
Q

NFκB-Dependent Signaling Pathway is activated by __ and __

A
  • tumor necrosis factor (TNF)
  • interleukin-1 (IL-1)
85
Q

NFκB-Dependent Signaling Pathway: Upon activation, __ and __ trigger a multiprotein ubiquitylation and phosphorylation cascade, leading to the release of __ from its inhibitory protein complex. Once released, it translocates to the __, where it activates the transcription of genes involved in inflammatory and innate immune responses.

A
  • tumor necrosis factor (TNF)
  • interleukin-1 (IL-1)
  • NFκB
  • nucleus
86
Q

The NFκB family includes proteins such as (5)

A
  • RelA
  • RelB
  • c-Rel
  • NFκB1
  • NFκB2.
87
Q

an inhibitory protein that tightly binds to NFκB dimers, keeping them in an inactive state within the cytoplasm of unstimulated cells.

A

IκB

88
Q

IκB is an inhibitory protein that tightly binds to __, keeping them in an __ state within the cytoplasm of unstimulated cells.

A
  • NFκB dimers
  • inactive
89
Q

The specific IκB proteins include (3)

A
  • κBα
  • IκBβ
  • IκBε
90
Q

NFκB activates the gene that encodes __, leading to the synthesis of __ proteins.

A
  • IκB
  • IκB
91
Q

Newly synthesized IκB proteins bind to NFκB, inactivating it and forming a __ feedback loop.

A

negative

92
Q

__-induced responses create two types of NFκB activity, leading to different patterns of gene expression. What are the two type of this activity?

A
  • TNFα
    1. Short TNFα Exposure
    2. Sustained TNFα Exposure
93
Q

A brief exposure to TNFα produces a single, short pulse of NFκB activation, turning on __.

A

gene A

94
Q

Prolonged TNFα exposure causes oscillations in NFκB activation, turning on __ (2).

A
  • gene A
  • gene B
95
Q

hydrophobic signal molecules that diffuse directly across the plasma membrane and bind to intracellular receptors (transcription regulators)

A

Nuclear Receptor Superfamily

96
Q

Nuclear receptor superfamily includes __, __, retinoids, and __, which diffuse directly across the plasma membrane to bind these receptors. Binding of these molecules to their respective intracellular receptor proteins __ the receptors’ ability to control the __ of specific genes.

A
  • steroid hormones
  • thyroid hormones
  • vitamin D
  • alters
  • transcription
97
Q

Nuclear receptors serve both as (2)

A
  • intracellular receptors
  • intracellular effectors
98
Q

Receptors within the nuclear receptor superfamily whose ligands are not yet identified

A

Orphan Nuclear Receptors

99
Q
  • __ bind to specific DNA sequences adjacent to the genes that the ligand regulates.
  • Ligand binding alters the conformation of the receptor protein, causing the inhibitory complex to __.
  • The receptor binds __ proteins that stimulate __.
A
  • Nuclear receptors
  • dissociate
  • coactivator
  • gene transcription
100
Q
  • What possess an internal rhythm that dictates different behaviors at different times of the day?
  • regulate cyclical changes in metabolic enzymes, such as those involved in the __ of humans.
A
  • Circadian clocks
  • sleep-wake cycles
101
Q
  • Internal oscillators that control diurnal rhythms.
  • enable organisms to anticipate regular daily environmental changes and take appropriate actions in advance.
  • function as timekeepers at the cellular level.
A

Circadian clocks

102
Q

cells in the suprachiasmatic nucleus of the hypothalamus that control diurnal cycles of sleeping and waking, body temperature, and hormone release.

A

SCN cells

103
Q

SCN cells receive cues from the __, which influence the __ and the rest of the body by releasing the hormone __.

A
  • retina
  • pineal gland
  • melatonin
104
Q

Circadian clocks have the ability to reset in response to __.

A

light

105
Q

In __, circadian clocks are similar to those in humans and can be reset by externally imposed light and dark cycles.

A

Drosophila

106
Q
  • Circadian clocks generally depend on __ feedback loops.
  • Oscillations in the activity of an intracellular signaling protein occur if that protein __ its activity with a long delay.
  • The accumulation of certain gene products switches __ the transcription of their own genes.
A
  • negative
  • inhibits
  • off
107
Q
  • In the circadian clocks, these proteins rise gradually during the day.
  • they form a heterodimer, dissociate, and are transported into the nucleus.
A
  • Tim (timeless) protein
  • Per (period) protein
108
Q

represses the transcription of Tim and Per genes

A

Per

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