Exam 2 Flashcards
(137 cards)
1
Q
Most of these are proteins
A
Secondary messengers
2
Q
Proteins on the cell membrane that receive signals and transduce it to the inside of the cell
A
Receptors
3
Q
This is what controls the relative numbers and positions of each cell types which is necessary to create normal tissue structure and function. This is done between the same cell types and different cell types.
A
Cell signaling
4
Q
All the decisions made by an individual cell must represent some sort of decision that is shared between the cells that resides in its neighborhood
A
Consensus
5
Q
This is what Src proteins are and they work in signaling programming and can transform cells
A
Tyrosine kinase
6
Q
EGF R and this consists of 3 functional domains in which part of the cytoplasmic domain shows homology with src
A
Epidermal growth factor receptor
7
Q
621 AA domain of EGF R and where the ligands bind
A
Ectodomain
8
Q
23 AA domain of EGF R and where the ligand binds
A
Transmembrane domain
9
Q
542 AA domain of EGF R and is where the src region of homology is
A
Cytoplasmic domain
10
Q
This is another receptor type with 3 functional domains; EGF receptor, tyrosine kinase domain (intracellular), and cysteine rich domain (extracellular).
A
Tyrosine kinase receptor
11
Q
This is formed on the EGF R following ligand addition
A
Phosphotyrosine
12
Q
This can occur when tyrosine kinase receptors dimerize and bind to an EGF molecule which will phosphorylate itself.
A
Transphosphorylation
13
Q
The two critical changes of tyrosine kinase receptors following ligand binding
A
Dimerization and phosphorylation
14
Q
Deletion of the ectodomain of EGF R results in this happening to the receptor
A
Activation
15
Q
An oncoprotein in avian erythroblastosis virus
A
V ErbB
16
Q
Some cancer cells will have deregulation of receptor firing that comes from receptor mutation/over-expression and this phenomenon
A
Ligand independent firing
17
Q
These are what can generate ligand independent firing.
A
Mutation or overexpression
18
Q
This causes constitutively dimerized receptors with a fusion protein and dimerization
A
Gene fusion
19
Q
These normally do not produce their own ligands and exhibit paracrine signaling, Ex: a mesenchymal cell will produce the ligand for an epithelial cell receptor
A
Normal cells
20
Q
What many cancer cells do and it is a form of signaling in which a cell manufactures its own mitogens. Ex: a cell has activation of a GF gene, secretes a ligand that binds to a receptor on the same cell.
A
Autocrine signaling
21
Q
This carries an oncogene (v sis) which is similar to PDGF (growth factor) which means that this virus can produce an autocrine signaling growth factor
A
Simian sarcoma virus
22
Q
The two major structures of a tyrosine kinase receptor.
A
EGF R and PDGF R
23
Q
The number of different proteins with EGF R and PDGF R structures in the human genome
A
59
24
Q
This is caused by abnormal dimerization of RTKs (tyrosine kinase receptors) which can occur via over-expression, mutation, truncation, and fusion of RTKs to other proteins.
A
Deregulated activation
25
Ordered sequences of biochemical reactions inside the cell with high specificity and speed. Mostly consists of proteins.
Signaling cascades
26
This encodes a homolog of the FGF R gene in fruit fly ommatidia
Sevenless gene
27
This is an upstream stimulator of Ras which functions downstream of the seven less gene.
Son of Sevenless (Sos)
28
This is a GEF (guanine nucleotide exchange factors). Turns GDP to GTP
Sos in fly
29
Tyrosine kinase receptor to Grb2 to Sos to Ras or to Shc before Grb2. Middle proteins are mainly connector proteins.
Signaling cascade of Ras
30
RTKs affect the physical location downstream components without necessarily changing their intrinsic activity
Localization model
31
RTKs
Tyrosine kinase receptors
32
This contains the SH1, SH2, and SH3 domains
Src protein
33
This is the catalytic domain of Src (kinase domain)
SH1 domain
34
This is the domain that binds to pY containing peptide. Composed of 100 amino acid residues and assembled from a pair of anti parallel beta pleated sheets surrounded by a pair of alpha helices
SH2 domain
35
This is the domain that binds to the proline rich sequence of the peptide
SH3 domain
36
This is what the SH2 domain works like since it recognizes both a phosphotyrosine and the side chain of amino acids (3 to 6 AA) that flank this phosphotyrosine on its C terminal side. The amino acid sequence determines the specificity for the substrates.
Modular plug
37
The number of distinct SH2 groups in the human genome
120
38
Bridging proteins that create intermolecular links in activating Ras
Grb2 and Shc
39
the type of protein that Ras is and is located on the inner membrane surface, active when bound to GTP
G protein
40
Guanine nucleotide exchange factor, converts Ras into its active form by replacing GDP with GTP
GEF
41
Ras intrinsic activity that hydrolyzes GTP to GDP
GTPase
42
GTPase activating protein that inactivates RAS by hydrolyzing GTP. An oncogenic mutation can inactivate this which leaves RAS continuously active
GAP
43
This interacts with at least three of the downstream effectors of Ras
Effector loop
44
MAPK, a downstream pathway of Ras.
Mitogen activated protein kinase pathway
45
MAPK pathway, PI3K pathway, and Real GEFs pathway
Ras downstream pathways
46
This is attracted from the cytosol by Ras and binds to Ras which causes a conformational change and activation of MEK
Raf
47
With the Raf conformational change, this phosphorylates both Try and Ser/Thr kinase which activates Erk
MEK
48
Extracellular signal regulated kinases that phosphorylate and activate transcription factors and other proteins
Erk 1 and 2
49
This can lead to certain cancers phenotypes like loss of contact inhibition, anchorage independence etc and can contribute to some cancers
MAPK deregulation
50
Phosphatidylinositol 3 kinase that synthesizes phosphatidylinositol triphosphate (PIP3) which attracts Akt/PKB and Rho GEFS.
PI3 pathway
51
Bad inhibition of apoptosis, mTOR stimulation of protein synthesis, and GSK 3B stimulation of cell proliferation
Result of PI3 pathway
52
This is activated by Ras and can convert PIP2 to PIP3
PI3K
53
These are located in a small minority of the head groups in the phospholipid bilayer
Inositol sugars
54
This is composed of two fatty acids with a long hydrocarbon tail, a glycerol, and a phosphate with an inositol
Phosphatidylinositol
55
These are tethered to plasma membrane
PI, PIP2, and PIP3
56
This cleaves PIP2 to yield diacylglycerol which activates protein kinase C (PKC)
Phospholipase C
57
This attracts and activates Akt/PKB and Rho GEFs by serving as a docking site for these three molecules in which once they are bound they are phosphorylated and activated
PIP3
58
This can inhibit apoptosis, stimulate cell division, and promote cell growth
Akt/PKB
59
This along with PI3K control the formation of PIP3
PTEN
60
The anti growth genes which are just as important as oncogenes
Turmor suppressor gene
61
1 in 20,000 children are diagnosed with this from birth to 8 years old
Retinoblastoma
62
This affects only a single eye, the sporadic form, less diagnosed, this requires two hits for tumor formation
Unilateral retinoblastomas
63
This affects both eyes, the familial form. This is more common to form a tumor. This requires one hit for tumor formation since there is one copy already inactivated by mutation
Bilateral retinoblastomas
64
Recombination that occurs during cell proliferation, this occurs more frequently than sporadic mutation in which a mutant allele can get on two chromatids, can lead to loss of heterozygosity
Mitotic recombination
65
Aka allelic deletion, a genetic alteration that converts a chromosome region from heterozygous to homozygous. Two chromosomes with a mutation or two chromosomes without a mutation. This happens the most frequent in cancer growth
Loss of heterozygosity
66
Happens more frequent than mitotic recombination and this is when a DNA polymerase will jump to a homologous chromosome during replication the jump back to the main template strand.
Gene conversion
67
This leads to a loss of a chromosome which can also cause a loss of heterozygosity
Chromosomal nondisjunction
68
This is what usually causes the first mutation and then loss of heterozygosity can amplify it
Sporadic mutation
69
There is a deletion of the 2nd and 4th bands of the 1st region in this chromosome in a retinoblastoma patient
Chromosome 13
70
There are mutations in this gene in retinoblastomas which plays an important role in cell division by being the molecular governor of the R point transition in cell cycling
Rb gene
71
This is what an unphosphorylated Rb binds to which prevents this from activating the transcription of genes coding for proteins required for DNA replication in S phase
E2F
72
This phosphorylates the Rb protein in cells stimulated by growth factors which prevents Rb to bind to E2F
CDK cyclin
73
Covalent attachment of a methyl group to a cytosine base which is an important mechanism to shut down genes. This is heritable and reversible and when this occurs in the vicinity of a gene promoter the expression of the gene can be repressed
DNA methylation
74
Methylation is found only when cytosines are located in a position that is 5' to guanosine
MeCpG
75
An important mechanism in deactivating tumor suppressor genes in tumors. Over half of the tumor suppressor genes that are involved in familial cancer syndromes are silenced by this.
Promoter methylation
76
The study of heritable changes in gene function that occur without a change in the DNA sequence
Epigenetics
77
These work together to shut down suppressor genes, one copy can be hit with the first and the second can be lost by the other.
DNA methylation and loss of heterozygosity
78
Form of colon cancer that is hereditary and it consists of the colon carpeted with hundreds of small polyps
Familial adenomatous polyposis
79
The pathway that controls colon cancer formation as well as other type of cancer formations by contributing to cell proliferation
Wnt B catenin
80
Bind of this substrate to the frizzled receptors causes inhibition of GSK 3B via disheveled and axon binding which prevents phosphorylation and degradation of B catenin. This leads to B catenin being present and promoting cell proliferation.
Wnt
81
In this condition, glycogen synthase kinase 3B (GSK 3B) phosphorylates B catenin which leads to the degradation of B catenin and cell proliferation halting.
Absence of Wnt
82
This associates with TF Tcf/Lef in the nucleus and drives cell proliferation
B catenin
83
The epithelial projections in the colon where colonic polyps form.
Villus
84
This can also lead to proliferation and colon cancer as it also works with B catenin
Apc mutation
85
The stem cells receive the Wnt signal from the stroma, B catenin interacts with Tcf/lef to promote stem cell proliferation, as stem cells move up the villus stimulation by Wnts decreases which leads to increased degradation of B catenin and cells enter apoptosis after 3 or 4 days.
Normal colon cell
86
Apc protein defects and B catenin levels remain high even in the absence of a Wnt signal, cells will stop migrating upward and accumulate within crypts to generate an adenomatous polyp.
Tumor colon cells
87
This contains multiple protein binding domains and the gene encoding this protein is frequently mutated which can lead to tumor growth. Key function is to bind to B catenin and down regulate its function in promoting proliferation
Apc protein
88
Gatekeepers and caretakers
Anti growth genes
89
Genes that directly control the biology of cells by affecting how they proliferate, differentiate, or die. Ex: tumor suppressor genes
Gatekeepers
90
Genes that control the biology of cells through maintenance of cellular genomes
Caretakers
91
How cells communicate with their surroundings
ErbB signaling network
92
The central governor of growth and proliferation located in the nucleus. Can send cells to G0 or the active cell cycle in which it can program the cell cycle phases. It is a network of interacting proteins that receives signals from various sources and integrates them to decide the cell's fate
Cell cycle clock
93
4 Phases of mitosis; prophase, metaphase, anaphase, and telophase. And 3 phases of interphase; G1, S and G2
Mammalian cell cycle
94
During this stage DNA is not visible with a light microscope
Interphase
95
Control mechanisms that ensure the fidelity of cell division in eukaryotic cells. These are essentially quality control systems. If requisites are met, cells are allowed to advance to the next phase.
Checkpoints
96
If genome is damaged after G1 entrance into S is blocked
G1, S checkpoint
97
DNA replication is stopped if genome is damaged
S checkpoint
98
Entrance into M is blocked if replication is not completed
G2, M checkpoint
99
Cell does not go into anaphase if the chromatids are not properly assembled on the mitotic spindle
Metaphase checkpoint
100
The point in time when the cell must make the commitment to advance through the reminder of the cell cycle through the M phase, remain in G1, or retreat into G0. This is close to the end of G1.
Restriction point
101
This is the period during which cells are responsive to mitogenic GFs and to TGF B
G1 phase
102
The regulatory subunits of the heterodimeric protein kinases that control cell cycle events
Cyclin
103
Aka CDKs, and are a group of serine/threonine kinases that are involved in the regulation of the cell cycle. The association of cyclins with these activates them.
Cyclin dependent kinases
104
These make up the engine of the cell cycle clock. The association increases the catalytic activity 400,00 fold.
Cyclin CDK complexes.
105
The four types of cyclin
A, B, D, E
106
The three types of cyclin dependent kinases
CDK 4/6, CDK2, and CDC2
107
This pairs with cyclins A and B
CDC2
108
This pairs with cyclins A and E
CDK2
109
This pairs with cyclin D
CDK 4/6
110
The cell cycle progression depends on the changes in this during the phases of the cell cycle
Level and availability of cyclin
111
This is relatively stable through the cell cycle
CDK level
112
During this cyclin B is high
Mitosis
113
During this nuclear D1 is high
G1
114
During this cyclin E is high and nuclear D1 drops
Beginning of S
115
During this cyclin A is high while cyclin E drops
End of S
116
Cyclin B rises during this through mitosis
G2
117
These strongly influence the levels of D type Cyclins
Mitogenic growth factors
118
These serve to convey signals from extracellular environment to the cell cycle clock in the nucleus during G1. Levels of this are influenced by extracellular signals, these can be growth factor signals, Wnts, cytokine, hedgehog, or other various ligands
D type cyclins
119
Where the cell cycle can be influenced the extracellular signals
80 to 90 percent of G1
120
During this, the cyclin cdk complexes in one phase of the cycle are responsible for activating those in the subsequent phase and for shutting down those that were active in the previous phase.
After R point
121
These are a group of proteins that affect the activities of cyclin CDK complexes
CDK inhibitors
122
4 INK4s that affect only CDK4/6 and three others that affect CDK2 and CDC2
Types of CDKIs
123
p16, p15, p18, and p19
4 INK4s
124
p57(kip2), p27(kip1), and p21(cip2)
The three others
125
This can strongly increase the expression of p15 INK4B, and slightly increase expression of p21(cip1)
The three others
126
This can strongly increase the expression of p15 INK4B, and slightly increase expression of p21(Cip1)
TGF B
127
This causes rapid increases in p21(Cip1)
DNA damage
128
The molecular governor of the R point transition. Contains 14 amino acids that can be phosphorylated. Dephosphorylation occurs at M by PP1 and through G1 it becomes phosphorylated unless it enters G0 which means it is not phosphorylated at the R point it is hyperphosphorylated.
pRb
129
These control the restriction point transition
Mitogens
130
At this point levels of cyclin E increased dramatically
R point
131
These complexes drive pRb hyperphosphorylation
E CDK 2
132
This is the inactive form
Hyperphosphorylation
133
When this binds to E2Fa it blocks their transcription activating domain. After hyperphosphorylation this will release E2Fs and allow them to work as transcription factors. As a cell enters into S phase the E2Fs are inactivated/degraded
pRb
134
This is what a phosphorylated pRb will bind to to repress transcription
Histone deacetylase
135
Control of this perturbed in most, if not all, human cancers.
pRb
136
The binding of E2Fs by pRb is prevented by some of these. Examples include Adenovirus E1A, SV40 large T, and human papilomavirus E7.
DNA tumor virus oncoproteins
137
Low expression of this has been linked to increased survival of breast cancer.
Cyclin E
