My MCM 2 Flashcards
(142 cards)
1
Q
3 Topological Compartmenalization
A
- Nucleus and cytosol (communicate through nuclear pore complex)
- Organelles in secretory and endocytic pathways (ER, Golgi apparatus, endoscopes, and lysosomes; communicate through vesicles)
- Mitochondria
2
Q
Protein Synthesis (overview)
A
- Ribosomes attach to the ER under the guidance of the amino acid sequence of the polypeptide chain being synthesized
- The mechanism by which secretory proteins are directed to the ER is explained by the signal sequence
3
Q
How does the SER differ from the RER?
A
- No ribosomes
2. Tubular cisternae
4
Q
SER functions
A
- Glycogen metabolism
- Lipid synthesis
- Phospholipid synthesis
- Detoxification
- Steroidogenesis
- Calcium regulation
abundant in cells that make steroids or lipids
5
Q
Golgi Apparatus functions
A
- Modification of carbohydrates attached to glycoproteins and proteoglycans
- Polysaccharide and oligosaccharide synthesis
- Synthesis of sphingomyelin and glycosphingolipids
- Sorting secretory products (marking lysosomal enzymes with mannose-6-phosphate
- Packaging and storing secretory products into secretory granules or vesicles
6
Q
Clathrin-coated vesicles
A
- Transport vesicles are coated by protein clathrin
- Seen in the exocytosis/secretory and endocytosis pathway
- In the endocytosis pathway, vesicles start the plasma membrane as clathrin-coated pits
7
Q
Dynamin
A
-surrounds the neck of the invaginated coated pit, causing the neck of the vesicle to pinch off from the plasma membrane
8
Q
Adaptin
A
-mediates clathrin binding to the vesicle membrane
9
Q
Central Dogma
A
DNA RNA –2->Protein
- Transcription
- Translation
10
Q
Genetic Code
A
-a set of rules that convert the nucleotide sequence of a gene into the aa sequence of a protein using mRNA as an intermediary
11
Q
- Start Codons
2. Stop Codons
A
- AUG (Methionine)
- UAA, UAG, UGA
for mRNA
12
Q
Silent Mutations
A
-a different codone is used than intended, but no consequences because it encodes for the same amino acid
13
Q
Missense Mutations
A
- a different codone is used, and it leads to the wrong amino acid being placed in the protein
- if the new amino acid is similar to the intended, no problem; if they are very different, big problems
14
Q
Nonsense Mutations
A
- codon changes to a stop codon, so the protein ends abruptly
- protein is either degraded or formed as a truncated version
15
Q
Frameshift Mutation
A
- one or more nucleotide are deleted or inserted into ORF (out of reading frame)
- leads to change in the codon sequence and consequently alteration in the amino acid sequence
16
Q
mRNA 3 parts
A
- 5 prime end (has 7 methly-guanines)
- coding region (contains blueprint and has codons)
- Poly (A) tail (tons of A residues)
17
Q
tRNA 2 parts
A
- 3’ CCA terminal region: Attached amino acid (AAs are esterfied to the CCA sequence)
- Anticodon loop: where codon on the mRNA binds
18
Q
Aminoacyl tRNA Synthetases
A
- catalyze the esterfication of amino acids to the CCA sequence on the tRNA
- Each AA has its own enzyme
- serve as the second genetic code
19
Q
Activation of Amino Acids
A
- Aminoacyl tRNA synthetase catalyzes additional AMP to COOH end of AA
- AA transferred to cognate tRNA
20
Q
Ribosomes: E vs. P
A
- E: 60s Subunit, 40s Subunit, and 80s Subunit
- 50 s Subunit, 30s Subunit, and 70s Subunit
- in P, it’s initiation factors (IF) and in E it is eIFs
* Use antibiotics to target P translational machinery*
21
Q
Ribosomal Complex
A
- A site: where the amino acid binds
- P site: where the polypetide is growing/where aminoacyl tRNA is attached
- Exit site: where tRNA leaves once it drops off its amino acid
22
Q
Translation Initiation
A
- Pre-initiator complex is assembled
- Large ribosome unit added to the complex
- A small initiator tRNA (which a GTP is bound to) attached to the P site of the small subunit
- The initiator tRNA-methionine complex is loaded onto the samll subunit of ribosomes on the P Site
- Other IFs are added
- Translation begins with initiation codon AUG
Requires hydrolysis of one GTP
23
Q
Translation Elongation
A
- An aminoacyl tRNA is loaded onto the ribosome in the A site through the actions and energy of elongation factors and GTP
- Peptide bond formatin between aa in A and P site catalyzed by peptidyl transferase
- energy comes from high energy bonds between aa and tRNA*
- *Requires hydrolysis of two GTP per amino acid added**
24
Q
Translation Termination
A
- Terminatin is triggered by stop codons
- Release factors bind to the A site
- Peptide chain released from the ribosomal complex and the latter dissociates into its components
Requires hydrolysis of one GTP
25
Polysomes
- clusters of ribosomes simultaneously translating a single mRNA molecule
- each synthesizes a polypeptide (makes synthesis much more efficient)
26
Tetracycline
* P elongation inhibitor*
| - binds to small 30s, locking entry of aminoacyl-TRNA to ribosomal complex
27
Chloromphenicol
* P elongation inhibitor*
| - inhibits peptidyl transferase
28
Clindamycin and Erythromycin
* P elongation inhibitor*
- binds to large 50s, blocking translocation of the ribosome
**erythromycin is commonly used to treat pertussis**
29
Streptomycin
* P elongation inhibitor*
- binds to 30s and interferes with the binding fmet-tRNA
- interferes with 30s associatin with 50s
30
Cycloheximide
* E elongation inhibitor*
- inhibits peptidyl transferase
- toxin for Streptomyces griseus
31
Diphtheria toxin
* E elongation inhibitor*
| - inactivates GTP-bound eEF-2, interfering with ribosomal translocatin
32
Shiga toxin and Ricin
* E elongation inhibitor*
| - binds to large 60s, blocking entry of aminoacyl-tRNA to ribosomal complex
33
Puromycin
* P/E Elongation Inhibitor*
- causes premature chain termination
- resembles the 3' end of the aminoacylated-tRNA
- enters the A site and adds to the growing chain
- forms a puromycylated chian, leads to premature chain release
- more resistant to hydrolysis
- stops the ribosome
34
Cytoplasmic Pathway
- for proteins destined for cytosol, mitochondria, nucleus, and peroxisomes
- protein synthesis beings and ends on free ribosomes in cytoplasm
- absence or presence of certain translocation signals play role in final targeting
*N terminal hydrophobic alpha helix goes to the mitochondria
35
Secretory Pathway
- for proteins destined for ER, lysosomes, plasma membranes, or for secretion
- translation begins on free ribosomes but terminates on ribosomes sent to ER
- first 20 amino acid residues of the polypeptide has ER targeting signal sequences (retention signal)
a. KDEL: for ER lumen proteins
b. Mannose-6-phosphate: for lysosomal proteins
c. N terminal apolar region: for membrane regins
d. Tryptophan domain: for secretory proteins
36
TOM vs. TIM
- Outer vs. Inner
| - Proteins must unfold to fit through these translocators, but heat shock proteins (HSP70) surround and protect them
37
Signal Recognition Particle (SRP)
- binds to the ER targeting signal and the ribosome during translation
- it wraps itself around the ribosome-mRNA-peptide complex, tethering it to the ER membrane and halting translocation temporarily
38
Chapernoes vs. Chaperonins
a. Chaperones: protect the protein and help fold into proper tertiary structure
- HSP70
b. Chaperonins: barrel shaped compartments that admit unfolded proteins and catalyze their folding in an ATP-dependent manner
- HSP60
39
Proteolytic Cleavage
- converts inactive forms to active enzymes by unmasking active site
ex. trypsinogen to trypsin
40
Glycoslyation
1. Post Translational Modificatin
2. extracellular proteins are glycoslyated (covalently linked to sugar residues in the ER lumen)
3. Can be either O-glycosidic or N-glycosidic linkages
a. O-links: are formed with hydroxyl groups of Ser or Thr residues
b. N-links: are always with Asparagine
41
Phosphorylation
1. Formation of an ester bond between phosphate and OH of an amino acid
2. Done by the activity of serine/threonine and tyrosine kinase
3. Phosphate removed by phosphatases
4. Regulates enzyme activity and protein function (particularly in signaling)
42
Disulfide Bond formation
1. Inter and intra molecular disulfide bonds stabilize many proteins
2. Bonds are formed between thio (SH) group of 2 cystein residues
3. Formation and reorganization of these bonds occurs in the ER lumen
* facilitated by protein disulfide isomerases*
43
Acetylation
1. Typically done on lysine residues and use acetly CoA as acetyl group donor
2. Done by HAT or HDACs
44
Post-transnational Modification of Collagen
- Lysine in collagen is modified to form 5-hydroxylysines
- ascorbic acid is essential for activity of lysyl and prolyl hydroxylases
- Defects in lysyl hydroxylases result in skin, bond, and joint disorders such as Ehlers-Danlors syndrome, Nevo syndrome, Bruck syndrome, Epidermolysis Bullosa simplex
45
Why are mitotic chromosomes condensed 500 times when compared with interphase chromosomes?
To prevent physical damage to the DNA as chromosomes are separated and passed on to daughter cells
46
Nucleosomes
The basic unit of chromosome packing
| -they are an octamer of histones, and DNA wraps around this
47
Euchromatin vs. Heterochromatin
1. Lightly bound; transcriptionally very active
| 2. Tightly bound; transcriptionally repressed; found around centromeres and telomeres often
48
Watson and Crick
1953: describe double helical structure of DNA
49
Nirenberg, Khorana, and Holley
1966: determine the genetic code
50
Human Genome project
- February 2001: the genome was 90% complete
- 2004: the genome was finished
- Interesting fact: only 1.5% of the genome was for protein coding sequences
51
RNAI
- microRNA folds back on itself, and the protein Dicer binds, cutting the RNA in to shorter segments
- miRNA pieces associate with a complex of proteins
- the target mRNA can basepair with the miRNA, and then degradation of the mRNA occurs (able to block its translation)
52
Introns
-99% of all introns begin with ...GT and end with AG...
53
Nuclear Receptor Superfamily: PXR
-xenobiotics
54
Hypermethylation
- typically down regulates transcription
- CpG islands at gene promoters acquire abnormal hypermethylation, which leads to transcriptional silencing, and this IS inheritiable (methylation of CpG islands stably silences genes (cancer/DNA repair genes))
55
DNA Polymerases require...
a primer with a free 3'-OH to begin processing
56
DNA Helicase
Unwinds DNA
57
Single Stranded DNA Binding Protein
- binds cooperatively to exposed ssDNA
| - helps to stabilize the unwound DNA and prevents hairpin formation
58
Topoisomerase
- relieves overwound supercoils
- called DNA gyrase in bacteria
- drugs that target this protein are anti-cancer drugs
59
Topoisomerase Inhibitors
- act as anti-cancer agents
- block the cell cycle
- generate single and double stranded breaks
- harm the integrity of the genome
- leads to apoptosis and cancer cell death
60
Depurination vs. Deamination
a. 5000 purine lost, bases/day
| b. C to U change, 100 bases/day
61
DNA Damage Caused by Chemical Agents
a. Crosslinking Agents
b. Alkylating Agents
a. Nitrogen mustard, cisplatin, mitomycin C, carmustine
| b. Dimethyl sulfate (DMS), methyl methanesulfonate (MMS)
62
Types of DNA Repair
a. Direct repair
b. Base excision repair
c. Nucleotide excision reapir
d. Mismatch excision repair
e. Recombination repair (non homologous end joining vs. homologous recombination)
f. Transcription coupled repair
g. Translesions synthesis (bypass synthesis)
63
Ataxia telangiectasia (AT)
a. phenotype: leukemia, lymphoma, gamma-ray sensitivity, genome instability
b. enzyme of process affected: ATM protein (a protein kinase activated by double stranded breaks)
64
BRCA2
a. phenotype: breast, ovarian, and prostate cancer
| b. enzyme of process affected: repair by homologous recombination
65
Fanconi anemia groups A-G
a. phenotype: congenital abnormalities, leukemia, genome instability
b. enzyme of process affected: DNA inter strand cross-link repair
66
CpG Sites vs. CpG Islands
a. random sites
b. promoters
*multiple methylated CpG sites in CpG islands of promoters stability silences genes*
67
Ubiquitin
a. exists in all E cells
b. attached to lysine residues on target proteins
c. then the protein is directed towards a proteasome, where it is degraded
68
SUMOlyation
-basically ubiquitin, but instead of added ubiquitin it adds SUMOs (small ubiquitin like modifiers)
69
The ligan-receptor complex ___ or ___ a cellular pathway.
1. activates
| 2. inhibits`
70
Endocrine Signaling
- a signal (hormone) is transported via the blood
- medium length of effect (minutes)
- travel a long distance to their receptor
- freely diffused signaling
- example: epinephrine (released by adrenal medulla acts no heart muscle)
71
Paracrine Signaling
- signal (paracrine factor) diffuses to neighboring target cell of a different cell type
- short lived signals
- example: testosterone (leydig cells synthesize and secrete testosterone)
72
Direct/Juxtacrine Signaling
- signal binds to signaling cell which then binds to receptor on the target cell
- the signal acts as a bridge
- example: heparin-binding epidermal growth factor
73
Hydrophillic Signaling
- cannot penetrate the plasma membrane, so receptors must be on the plasma membrane
- signaling molecule-receptor complex initiates production of second messenger molecules inside the cell (downstream cellular response)
- generally small and derived from AA, polypeptides, or through lipid metabolism
- shorter half lives (seconds to minutes)
- Receptors involved: GPCRs and RTKs
74
Lipophillic Signaling
- pass through plasma membrane of target cell and binds to receptor proteins inside the cell
- signaling molecule-receptor complex acts as a TF
- long half live (hours to days)
- Families of DNA binding TFs: cytoplasmic receptors and nuclear receptors
75
Three Types of Receptors
1. Ligand-gated ion channels (nAChR, GABA, 5-HT3, GlyR)
2. G protein coupled receptors (GPCRs)
3. Enzyme-coupled receptor class (receptor tyrosine kinase (RTKs))
76
GPCRs
1. Extra cellular domain binds to signal
2. Trans Membrane Domain is composed of 7 alpha helices
3. Intracellular Domain interacts with G proteins
77
Active vs. Inactive G proten
a. active proteins have GTP
b. inactive proteins have GDP
-exchange is done by guanine nucleotide exchange factor
78
Variations in GPCR Signaling
1. Gs (stimulates adenylate cyclase; epinephrine/histamine)
2. Gt (stimulates cGMP phsophodiesterase; light)
3. Gi (inhibits adenylate cyclase; epinephrine/norepinephrine/dopamine)
4. Gq (activates phsopholipase C; acetylcholine)
*REVIEW SLIDE AND READ IN BOOK*
79
Hydrolysis of cyclic nucleotides (CB)
1. cAMP phsophodiesterase: hydrolyzes cAMP to AMP
2. cGMP phosphodiesterase: hydrolyzes cGMP to 5'-GMP
3. Inhibitors of cGMP PDE increase concentration of cellular cGMP, leading to smooth muscle relation and vasodilation (viagra)
80
Nitric Oxide and smooth muscle relaxation(CB)
- NO is produced in epithelial cells and is responsible for the relaxation of smooth muscles
- NO diffuses to neighboring muscle and activates guanylate cyclase, leading to the production of cGMP
81
Inhibitors of G proteins by bacterial toxins (CB)
- cholera toxin prevents the inactivation of Gsa and pertussis toxin prevents the activation of Gia
a. cholera: covalent modification of a subunits ADP ribosylation of ARG, decreases GTPase activity; Gsa remains active and continuously stimulates adenylate cyclase, resulting in overproduction of cAMP
b. pertussis: ADP ribosylation of CYS on Gia prevents activation of dissociation of a subunit from the G protein complex; less inhibition of AC and overproductin of cAMP
82
GRKs
- G protein receptor kinases
| - they phosphorylate the GPCRs
83
RTK
-Receptor Tyrosone Kinase: has an extracellular domain to serve as the signal binding site and an intracellular domain that possesses tyrosine kinase activity
84
Binding of ligand to the ECD of RTKs leads to...
- dimerization
| - dimerized receptor phosphorylates tyrosne residues
85
RAS and cancer (CB)
- mutant forms of RAS, or its GEFs or GAPS have been implicated in wide range of human cancers
- RTKs are the target of pharmacological inhibitors; excessive signalling from mutated/over expressed RTKs is associated with cancer
86
What can hybridization and PCR answer?
1. They can identify the disease causing organism
| 2. They can diagnose inherited disorders in humans
87
Hybridization
a. ssDNA binds to another strand of DNA or RNA with complementary sequence to form a hybrid
b. can detect/quantify target DNA or RNA
- ex. southern blotting and northern blotting
88
Southern Blotting
- both probe and target nucleic acid are DNA
| - labeled with radioactive or fluorescent tag
89
Northern Blotting
- probe single stranded DNA and target is mRNA
| - labeled with radioactive or fluorescent tag
90
Polymerase Chain Reaction
a. dsDNA is denatured to ssDNA
b. Primers are designed to complement sequences that flank each end of DNA in 3'-5' direction and they anneal to the DNA
c. Taq polymerase synthesizes copy of the DNA
91
Taq Polymerase
- synthesizes copy of DNA by extending the primers on both ends
- DNA doubles in each cycle and becomes greatly amplified
92
Cell Free Cloning PCR
- amplify isolated DNA regions
| - used for earlier detection of microorganisms and specific genetic mutations
93
Quantitative PCR
- used to quantify copy number of a specific gene in two or more samples in real time
- includes a probe which fluoresces only in the presence of the PCR product
- used to detect levels of infectious agents and to determine levels of gene expression
94
Restriction fragment length polymorphism
- individual genomes differ by 1 in every 1000 base pairs
- and when these occur in recognition sequences for restriction enzymes different fragments are produced, and this can be used to distinguish between people
- can also be coupled with electrophoresis and southern blotting to detect mutations
95
Variable number of tandem repeats
- pattern of shorter tandem repeats occurs in genome, but varies in individuals
- VNTR repeat regions are isolated from genomic samples by flanking restriction sites or through PCR
- identifies and determines severity of inherited diseases like Huntington
96
Recombinant Proteins
- large scale production is used to make medicine (like insulin)
- cDNA of the protein is inserted into expression vectors , and the host replicates a lot producing more of the desired product
97
Normal human insulin has Proline at position __ and ___ at position 29 at _ terminus of _ chain
1. 28
2. Lysine
3. C
4. B
98
Production of Antibodies
- spleen cells are paired with myeloma cells (tumor cells) to produce hybridomas
- the hybridomas are cultured in HAT medium, and the positive cells are selected, and the monoclonal antibodies are harvested
99
Enzyme-linked immunosorbent assay (ELISA)
-immunological technique which tests for the levels of specific antigen or antibody concentrations in biological samples using a corresponding antibody or antigen
100
Indirect ELISA
- measures the amount of an antibody in a sample
| - coat the plate with antigen
101
Sandwich ELISA
- measures the amount of an antigen in a sample
| - coat plate with antibody
102
Diagnosing HIV
- done by INDIRECT ELISA
| - specific antibodies to HIV are produced in humans 4-6 weeks after infection
103
Diagnosing MI
- done by SANDWICH ELISA
- cardiac forms of troponin type T and I increase in acute MI
- the antigen is coming from the heart cells
104
ELISA Pregnancy Test
a. Reaction site: free hCG antibodies bind to hCG in urine and complex moves to the test site
b. Test site: has immobilized hCG antibody hCG/ab complex from reaction site binds to immobilized hCG antibody (sandwich is complete--dye gives color)
c. Control site: a non-specific antibody immobilized; dye gives color regardless of +/- of hCG (confirms the test is working)
105
Western Blotting
- used to detect the levels of a target protein
- SDS-PAGE: separates out the proteins on a gel by applying an electrical field
- proteins migrate based on size
- transfer proteins from gel to nitrocellulose membrane to make them surface exposed
- add primary antibody
- add secondary antibody
- secondary antibody has an enzyme tage
- add substrate
- gives color
* used to confirm HIV
106
Banding and Nomenclature of Chromosomes
a. Arm: p is the short arm, q is the long arm
b. Region: 1 is near the centromere, 2 is near the telomere
c. Band: 1 is closer to the middle of the arm, 2 is closer to the edge of the arm (by the telomere)
d. Subband: numbers increase within each band as they go towards the telomere
107
Two ways Meiosis creates genetic diversity
a. Random segregation of homologs
| b. Cross-over exchange
108
Hardy-Weinberg Principle
- specifies the relationship between gene frequencies and genotype frequencies
- useful in estimating gene frequencies from disease prevalence data and in estimating the incidence of heterozygous carries of recessive disease genes
- equation: p^2 + 2pq + q^2 = 1
109
M Phase
- Nuclear division (mitosis) at the beginning
| - Cell division (cytokinesis) at the end
110
Interphase
- G1: RNA and protein synthesis needed for DNA replication
- S: DNA synthesis
- G2: DNA stability check
111
Go
- not actively dividing cells
| - can happen due to poor nutrition/environmental conditions-->cells withdraw from the cell cycle
112
1 Restriction point and 3 Check point
a. if growth factors are limiting --> restriction occurs; two hours prior to S phase (you need the presence of growth factors to move past the Restriction point)
b. G1 checkpoint: similar timing to restriction point; occurs in response to DNA damage (fix it prior to replication)
c. G2 checkpoint: verify complete genomic duplication
d. M checkpoint: ensures chromosomes attached to mitotic spindle
113
3 Ends of Cell signaling
a. Proliferation
b. Differentiation
c. Apoptosis
114
Retinoblastoma and Cyclin Activity
a. When unphosphorylated, Rb binds to E2F
b. Cyclin D-CDK4 and Cyclin D-CDK6 lead to Rb being hyperphosphorylated
c. E2F is free, and this leads to G1-->S phase
115
Cyclin-CDK Protein Complex
a. Cyclins: proteins that interact with and regulate CDK's activity
b. Cyclin/CDKs drive phosphorylation of specific substrates (ex. Rb)
c. Activation: binding of cyclin to CDK causes partial activation; full activation requires CDK-activating kinase (CAK)
d. Inhibition: CDK inhibitors (p27 or WEE1) inhibit the cyclin-CDK complex; inactivates the kinase activity of cyclin-CDK
116
Cyclins-CDK for G1 phase
1. Cyclin D-CDK4
2. Cyclin D-CDK6
(helps the passage of cells through the R point in late G1 phase)
inhibited by: CIP/KIP adn INK4
117
Cyclins-CDK for G1/S phase
1. Cyclin e-CDK2
inhibited by CIP/KIP
118
Cyclins-CDK for S phase
1. Cyclin A-CDK2
inhibited by CIP/KIP
119
Cyclins-CDK for M phase
1. Cyclin A-CDK1
| 2. Cyclin B-CDK1
120
p27
- cdk inhibitory protein
| - binds to the whole complex to inactivate it
121
Anaphase-Promoting Complex/Cyclosome (APC/C)
- key regulator during mitosis
- member of ubiquitin ligase family of enzymes
- activated by binding to Cdc20
- works to ubiquinate cyclins to get their levels to drop
122
p53
- a transcription factor that is normally inactivated through degradation by E3 ubiquitin ligase
- activation leads to increased transcription of p21
123
p21
- cyclin-dependent kinase inhibitor
- mainly associated with inhibition of CDK2
- major target of p53 activity
124
Intrinsic Pathway
- mitochondrial dependent (cytochrome c)
- occurs in response to injury, DNA damage, lack of oxygen/nutrients/extracellular survival signals
- eventually merges with extrinsic pathway
125
Extrinsic Pathway
- mitochondrial independent
| - eventually merges with intrinsic pathway
126
Caspase Activation
- protease that mediates apoptosis
- first synthesized as an inactive precursor (procaspase)
- activated by protease cleavage and is a heterodimer
127
Two classes of Caspases
a. Inhitiators: Caspase 8 and Caspase 9, which help to activate Caspase 3
b. Executioners: destroy their target; execute apoptosis; Caspase 3
128
BAX
- Pro-apoptotic, BCL-2 family
- distributed throughout the mitochondrial membrane
- stimulus for apoptosis
- aggregates and forms a channel so cyclin can move to cytosol and start apoptosis
129
Apoptosome
-APAF-1 joins with cyclins to form the apoptosome, which then activates procaspase 9
130
Proto-oncogene vs. Oncogene
a. normal; expression by GFs, receptors for GFs, TFs, and signal transducers
b. cancerous; gain of function; expression leads to increased expression of protein products, expression of altered protein that does not respond to normal signals
131
Gain of Function mutations
a. point mutation
b. deletion
c. gene amplification
d. chromosomal translocation
132
HER2
- Val to Gln mutation leads to overexpression of Her2
- causes receptors to act like they're binding all the time
- leads to breast cancer
133
Tumor Suppressor Functions
a. repress cell cycle progression
b. promote apoptosis
c. couple DNA damage to cell cycle
d. DNA repair proteins (BRCA)--> decreased DNA repair-->increased inactivation of tumor suppressors-->activation of oncogenes
134
Tumor Suppressor Examples
a. RB1 gene encodes pRB protein
b. TP53 encodes p53
c. PTEN
d. APC
135
Hallmarks of Cancer cells (10)
1. Self-sufficiency in growth signals
2. Evading growth suppressors
3. Activating invasion and metastasis
4. Enabling replication immortality
5. Inducible angiogenesis
6. Resisting cell death
7. Deregulating cellular energentics
8. Avoiding immune destruction
9. Tumor promoting inflamation
10. Genome instability and mutation
136
Viral Oncogenes
- viral genome inserts by the proto-oncogene
- and it gets replicated and taken to other cells
- if mutation occurs, leads to oncogenes in other cells
137
Sites of Action of Chemotherapeutic Agents
1. Alkylating Agents (affect all phases of cycle)
2. Antimetabolites
3. Topoisomerase Inhibitors I and II
4. Cytotoxic Antibiotics
5. Mitotic Inhibitors
138
Herceptin
- antibody directed towards HER2
| - used for breast cancers that over express HER2 or HER2 mutations
139
Gleevec
- used to treat CML (must take pill everyday for the rest of their life
- Gleevec sits in ATPs pocket, so the target protein is not phosphorylated
140
Recombinant Proteins
-large scale production of recombinant portions
A. Insulin
B. Growth hormone
C. Erythropoietin
D. Clotting factors
E. Vaccines against flu, malaria, viral infections
-cDNA of proteins is inserted into expression vectors
141
Cyclin-CDK associated with G1
Cyclin D with CDK 4 and CDK 6
| -they help the passage of cells through the restriction point in late G1 phase
142
Roof site vs. Cave site
1. both are found on CDK
2. Cave site phosphorylation activates the cyclin-CDK complex
2. Roof site phosphorylation inactivates it (done by wee1)
