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171 Cards in this Set
- Front
- Back
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Regation can affect final protein concentration, but what is most common point of regulation
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transcription
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What is thyroid hormone an example of
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transcriptional regulation
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Thyroid hormones (T3,T4) stimulate energy yielding metabolism by activating
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genes that encode for key catabolic enzymes
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The throid homres are produced in the throyid gland, but the singal to prodcue them is from
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the hypothalamus
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What is the synthetic version of T4, and why only T4
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T4 is more stable--synthroid
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T3 and T4 are both secreted by the thyroid, but what is the major and where is located mainly
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T4, major product in bloodsteam
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Upon entry into traget cells what happens to T4
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converted to T3, the utimate biologically acitve form
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Thyroid receptors have a much higher affinity for
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T3
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Both T3 and T4 are used to treat
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hypothroidism
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Synthroid is the commonly used sythnetic, is an sterioismoer of, how is metabolized
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Thyroxine, metabolized more slowly, and needs only once a day administration
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What do thyroid hormones interact with
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Thyroid receptors (TRs)
TR-alpha TR-beta |
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What type of transcripton factors does thyroid hormone have
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"ligand-dependent"
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THe thyroid hormones binds to the Thyroid receptor a or b, and then it binds to , which are located
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TRE (thyroid response elements) located within the promoter DNA
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The thyronines act on the body to do what 3 things
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1. increase basal metabolic rate
2. affect protein syntheiss 3. increase body's sensitivity to catecholamines (adrenaline) |
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How do the peptide hormones function differantly then insulin or epinephinre,
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insulin--can pass through membrane so binds to receptor outside of cell, uses 2nd messenger--FAST response, then steriods or thyroid--SLOW
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What are TRE usually located
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near 5' ends
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What does unligand TR boudn to TRE o f a paricular gene cause
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repression of gene expression
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What is TRE
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sequences of DNA in promoter region that have either a positive or negative influence on gene expression
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What happens with T3 binds to TR
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Liganded TR binds to TRE which causes gene expression
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What does degree of responsiveness to thyroid hormones depend on
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cell, number of TRs, specific TRE's and nuclesar T3 concen
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What are whats to regulate gnene expression post-transCRIPTIONAL
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SAARS
1. stabily or mRNA 2. accsibility to translatio 3. ability of ribosomes 5.rate of translation 6.rate of re-inination 7. stability of protein produ t |
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How can different mRNA be degraded at such different rates
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1. speicifc nucleases "attack" to degrade
2. RNA has binding site for protein to protect it |
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IS mRNA stabiltiy regulated
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YES
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How are iron levels reulgated
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POST-transcriptional regulation
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Iron is an essential but toxic metal, thus its concentration in highly regulated HOW
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proteins Ferritin, and Transferrin receptor
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What does Ferritin do, and where is it regulated
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sequesters iron intracellularly, regulated at level of mRNA translation
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What does (TfR)Tranferrin receptor do, and where is it reglation
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scavenges iron extracelular for import, reulgation at level of mRNA stability
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What happens if iron levels are TOO higher
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Raise Ferritin (sequesters), and LOWER TfR (no need to bring more in)
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What happens if iron levels are too LOW
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lower ferritin, and RAISE TfR to bring in more iron
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How is Ferritin levels reulated
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mRNA translation and
IRE-BP--iron response elememnt binding protein |
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What happens to Ferritin in high levels of iron
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iron binds to IREBP, prevent from binding to mRNA--to so have increase translation of ferritin mRNA
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What happens to Ferritin in low levels of iron, and what can't bind
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IREBP binds to IRE on mRNA and blocks iniation of translation--40s ribosome cannot bind
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When does IREBP have a low affinity for IRE in 5'
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when iron levels are high, which allows iniation of translation
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Where is the IRE location in ferritin mRNA
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in the 5' untranslated region (UTR)
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Where are the IRE located in TRANSFERRIN receptor
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in the 3' untranslated region (UTR)
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When IREBP has a low affinity for IRE in 5' what happnes
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have high iron level, so iron binds to IRE-BP, and transferrin receptor mRNA is degraged
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What happens in IRE-BP binds to 3' IRE UTR
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prevent 3' UTR from being broken down by nucleases, and lead to Transferrin receptor translation , and increased levels or TR
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What happens to transferrin receptor when iron levels are high
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iron binds to IRE-BP, and it is released from IRE's, and then transferrin receptro mRNA is degraded, and no receptor is made
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What can viral infections due to host translation
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SHUT it DOWn
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What enzyme do viruses use to shut down host translation
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uses protease that cleaves EIF4G
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What happens if there is no EIF4G
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no CAPPING, then iniation factors cannot bind, and ribosome cannot bind to find AUG
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Are viral RNAs need caps
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NO
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What is a tumor
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a growing cluster of cells
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A non-life threatening tumor is
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benign
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What life-threatneting tumor is
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maligant and cancerous
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Maligant tumors can leave primary mass and spread throughout body known as
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metastasis
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What is a sarcomaa
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tumor in connective tissue
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What is carcinoma
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turmor in epithelial tissue
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What is lukemia
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tumor in blood cells
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What is lymphoma
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tumor in lymph nodes
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What are cancer-causing agents
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carcinognes
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Many cancinogens are also
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mutagnes
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Some cancers may be caused by mutaions, althought tumors can also arise from
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viral infection
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Mutations in only a FEW gens can cause cancer--primarly genes involved in
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cell cycle control
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What is cell division regulated by
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a family of extracellular GROWTH factors
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What are extracellular growth factors
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released by proto-oncogenes that cause cells to divide and differntiate
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Defects in regulation or recognition of growth factors can lead to
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Oncogenes
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What are oncogenes
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proteins that release defecitve growth factors, lead to uncontrolled growth--aka CANCER
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How does an oncogene form froma viral infection
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during viral infections that DNA seqence of a proto-oncogene is copied, and incorporated into genone, and b/c mutated
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What happens when this viral oncogene is expressed
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the abnormal protein interfere with regulation of cell growth
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The oncogenic defect can be in any of the proteins involved in
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sending the "divide" signal to the cell
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Can the defect be in secreted proteins, GF, transmembrane proteins, cytoplasmic, and nuclear transcription factors
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YES
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Proto-oncogenes can b/c oncogenic without a viral intermediary how
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chromosonal reagreeamnets, chemcial agents, and radiation
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What is EGF
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epidermal growth factor
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What is ErbB
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lacks EGF binding domain, so it is ON, an telling cell to divide regardless if growth factors present or NOT
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ErbB mutatant is commonly assoicated with glandular cancers such as
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breast, ovart, and stomach
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What are tumor suppressor genes
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NORMAL cellular genes that BLOCK or limit cell division
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What to proto-oncogenes do
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ACTIVATE cell division
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Remember that cancer is a mutistep MUTATION process which means
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mutiple controls must be inactivated to iniate cancer
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MUST cancer involve SEVERAL genes
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YES
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What portions of protein can undergo modification
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amino terminus, internal and carboxy terminus
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In PROKS the N-terminal formyl group is removed by
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deformylase
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How is teh N-terminal Met residue removed
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enzymatically to form final protein product
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Is the N-terminal residue acetylated in approx 50% of EUKS
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YES
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What is hydroxylation
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internal modification
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What is importance of proline hydroxylation
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4-hydroxyproline plays a central role in folding of collagen
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What happens when you have a vitamin C deficieny
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cofactor for hydroxylase, and cannot hydroxlation proline, which results in survy
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What does phosphorylation/dephosphorlation do
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acts as a molecular switch
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Protein kinases are often targets for
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phosphorlation
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Is phosphorlation REVERSIBLE, and COVALENT
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YES
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What three aa are substrates for protein kinases
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Serine, Theronine, and Tyrosine
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What can protein kinases do
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signal amplication, cascade signal
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Gleevac, Iressa, and Tarceva are examples of
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protein kinase inhibitors
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What does protein kinase inhinitors target
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the ATP binding regions of protein kinases
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What are phosphatses
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remove a phosphate
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What are 3 classes of phosphatases
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1. Tyrosine phosphatases
2. Serine/Theronine phophatase 3. Dual specificity phosphatase |
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What do dual specficiy phosphatases do
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dephosphorlate both Ser/Thr and Tyr residies
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What does inhibition of phosphatase activity do
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prolongs signal
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Post-translation modification of proteins occurs in the
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ER
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What do ER and assoicated ribosome synthesize
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membranes and secreted protiens that are HIGHLY glycostlated
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What do free ribosome synthesize
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proteins that are not glycoslated
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What is glycosylation
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that the membrane and secreted proteins have a carbohydrate side chain attached
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Most membrane and secreted proteins with a sugar side chain attached are called
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glycoprotein
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Attachment of a glycoprotein to a Asn residues forms
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N-linked oligosaccharides (attachd to amino acid)
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Attachment of a glycoprotein to a Ser or Thr resdiues forms
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O-linked to oligosccahrides
attached to a hydroxy group |
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Where does glycosylation occur
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in the ER and Golgi appartaus
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N-Linked oligosacharids contain a common core of
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2 N-acetylglucosamines, and 3 mannose residues
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O-Linked olgiosaccharids contain a core of
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variable Ser/Thr residues to N acetylGALACTOsamine
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Glycoproteins are rich in information, they preform cell-cell communication and act as
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binding site for viruses and bacteria
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Are atibodies and receptors high glycosated
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YES
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Do glycoproteisn influence the stability of enzymes and peptides
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YES
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Do glycoproteins play a role in the catalytic activity of proteins
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NO
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What is eryhtopoietin
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made by kidenys in resonse to reducued oxgen, makes RBC
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Glycoprtein produced genetically in CHO (chinease hamster orvary) and used in treatment of
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doping of althetics, and neutropenia, and anemia
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Is the glysylation pattern of EPO different than in CHO
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yES
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What is isopreylation
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addition of isprenyl groups makes proteins more hydroPHOBIC
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What is isporene an intermediate in
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cholesterol synthesis
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What is Farnesylation do
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A Farnesyl group with an isoprene attached makes more hydrophobic, helps better anchor PROTEIN to membrane
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What aa form disulfide bond formation
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cystein
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What does disulfide bond formation help do
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helps protect and maintain folding folding and secondary and tertiary stcuture
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Can some proteins be denatured and renatured SPONTANEOUSLY
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YES
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Some proteins need help of enzymes to correctly fold, 2 are
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1. Protein disulife isomerase
2. Peptide Prolyl cis-tran isomerase |
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What does Protein disulfide isomerase to
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breaks and forms disulifed bonds UNTIL correct bonds are formed
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What does Peptide porly cis-trans isomerase do
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converts cis and trans isomers of Proline peptide bonds
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While some proteins correcly fold spontenosuly, some proteins are prevent from spontanesous folding by interacting with
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Chperone proteins
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What do chaperone prteins do
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prevent MISFOLDING
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Heat Shock Proteins utilize what type energy to prevent protein misfolding
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ATP
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HSP 90 are used as
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ANTI-cancer drugs
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How are proteins synthesized in the ribosome targeted for delivery to ER mitochorndira or nucleus
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they have signal seqncenc located at the N-terminal of the PROTEIN
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What is the N-terminal seqencue is the protein is targeted for the ER
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13-36 AA
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What is the N-terminal sequence is teh protein is targeted for the mitchondria
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20-25 AA
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What is the mechanism for ER Targeting
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The signal sequence is first thing made in protein, so a SRP (signal regontion particle binds, adn halt elongation--it then binds to SRP receptor
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What happens are it binds to it receptor
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the polypeptide is release in ER though petide translcation complex, adn elgongation continue
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What is last step of ER targeting
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The signal seqencue is removed by sinal peptidase
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How does a protein reach the nuclues, and where is it located
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by a Nuclear Localization signal--internal sequence
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Once the protein reaches the nucleus is the singal cleaved
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NO---b/c nuclear pore contasly breaks down
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Proteins leave the cytosol and enter
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ER where glycosation can occur
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Where do proteins go after ER
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enter in Golgi apparitsu on cis, leaves trans where they are sorted in Secretory or transport veiscles
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What happens to secretory granules
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exported
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What hapesn to transport vesicles
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fuse into membrane
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What is different about how proteins are targeted for mitochondria
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The entire protein is synthsized, then N-terminal signal binds with HELP of chaperone proteins binds to mitochondrial membrane
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What role do chaperones play in mitrochondrial targeting of proteins
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Guide FULLY synthsized protein to mitochondria, and prevent folding
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The proteins is then shuttled across membrane through translocater protein, once inside what happens
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fold by HSP proteins, and singal peptidase removes the singal sequence from teh N-terminus
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What are 2 mechanism of proteins can enter the nuclear pore
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1. Passive diffusion
2. NLS mediated import (larger) |
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How can protein enter nuclear pore by passive diffusion
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if its UNDER 65,000 Daltons
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What is mechanism for protein to enter if greater than 65,00 Daltons
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THE NLS binds to an importin receptor IN CYTOPLASM, and the complex enter through nuclear pore complex, protein release and importin returns back to cytoplasm
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What type of subunits does importin receptor have
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alpha and beta subunits
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What is the NLS sequence rich in
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ARG or LYS residues
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Do protein half-lives range from 30 sec to many days
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YES
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SMALL Strucutral proteins have what type of half-life
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LONG-half life
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LARGE Regulatory proteins have whawt type of half-life
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SHORT half life
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What is N-Termial rule
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Certain N-terminal a.a. target the protein for degration
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What amino acids are destabilzing where half life is only 2-30 minutes
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HAL, Phe, Trp, Try, and Ile
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What is ubiquitinatoin and preteasonal degration, and who does it occur in
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MAJOR cytosolic pathway for degration of proteins in EUKS
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What does ubuquitination and proteasoma degreation do
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1. degrade old and damaged protein
2. misfolded proteins 3. serves as regulatory function by degraed regulatory protein |
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Is ubiquitin a small protein with a higly conserved AA sequence, and example
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same in humans as yeast
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How does ubiquin b/c convalentyl attached to target protein
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carboxy group glycine attaches to lysine of target protine
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What is isopeptide linkage
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how GLY and LYS are attached
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What are 2 steps of ubiquitination
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1. Acitvation of UB by EI, and then Ubiqutination
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What happens after ubiquination
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degraded the the 26S proteasome
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What shape is the 26S proteasome
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barrel shape
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What can also target regulatory proteins for ubiquitinato and proteasomal degration
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phosphorylation
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Can proteasome inhibitors be anti-cancer drugs
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YES
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What is the N-terminal rule and it ONLY assoication with ubiquitnation
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the N-terminal a.a. is a target for ubiquitination
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What is protelytic activation and activated by
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start with inactive precursor (zymogen), then peptidase activates and removes reglatory enzyme
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What when trpysin is release form the pancrease
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in inactive form, then undergoes protelytic activation
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What is the Caspase Cascase, adn what causes it
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cell death by proteases
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What is Caspase
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Cystein-dependent Aspartrate specifc protease
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Is the Caspase constitutively expressed, and regulated
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POST-transcriptioanl
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How are executionar caspases acivated
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cleaved by iniator caspase, to b/c active
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Where does cleavage of executior caspases occur
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C-terminal of 2 asp resisue
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What is active caspase
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heterotetramer
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Why is protein transport and degradtion important
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prevents protein aggregtion of misfold or damaged proteins
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What is prion disease an example of
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neurodegenerative disease associted with protien aggregation
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Is a prion infection, and causes NO IMMUNE response, why
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smaller the virus, abnormal protein
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Do prions have genetic material/nucleic acid, and how do they replicate
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NO genetic material, replicate by converting normal prion into abnormal prion by changing shape
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What is abnormal prion protein
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PrPsc
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What is Prp
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prteinacous infectious particfle
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Where do Normal cells expres PrP (glycoprotein)
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on the surface of plasma membrane
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What happens is PrP b/c exposed to Prpsc
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causes a confomation change from alpha helis to small beta sheets, forms lots of PrpSc, aggregate, adn lead to death
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What other factors enchance protein aggregation
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genetic-SNP
and environment--oxidatve damage to protine |
