6.11 Transforming cells Flashcards Preview

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Flashcards in 6.11 Transforming cells Deck (54):
1

acute vs weak transforming viruses

acute transforming viruses transform cells quickly at low dose

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transforming viruses are

retroviruses

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why do acute transforming viruses transform cells better?

they have src region in thir DNA like in ATV --first proposed oncogene

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src

rous sarcoma virus - rats

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ras

harvey sarcoma virus

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myc

maloney sarcoma virus - mice

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sis

simian sarcoma virus

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fes

feline sarcoma virus

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viral oncogenes were found in malignant and normal cells bc

transforming retroviruses evolved by picking up mammalian genes and incorporating them into their genome -- picking up a gene that makes the cell immortal makes the virus immortal

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human dna fed to mice cells use Ca salt showed

loss of contact in hibition and tumor growth, with greater efficiency each time experiment was repeated with tumor DNA

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conclusion of contact inhibition mouse cell experiment

the v-ras gene caused the tumor but there was no virus! This means that the gene was simply a mutated mammalian gene, differing on the 12th AA from glycine to valine

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ras is a

signal transduction protein - it is a GTP dependent protein, active when bound to GTP, has intrinsic GTPase activity, inactive when bound to GDP

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ras is involved in

many function including cell replication

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Ras is held to the membrane by

a farnesy membrane anchor and is linked to a growth factor receptor by a bridging protein

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activated ras binds

Raf-1, GAP, and activates the Map kinase path, that activates transcription, that activates the myc gene, leading to cell cycle progression

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the G to V mutation in v-ras causes

reduces the GTPase activity so ras is locked in the "on" position -->abnormally active signalling for growth

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why was ras the first oncogene discovered by random transfecting of DNA?

Ras is the most common activated oncogene encountered in human tumors. Not the most common gene affected, that's p53

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what is a good drug target against v-rase

the farnesyl membrane anchor -- farnesyl transferase inhibitors might take away the capacity for ras to bind the membrane so it won't be able to effectively transduce the signal

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NF-1 tumor suppressor gene

GAP protein that binds to ras before map kinase path activation

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Molecular basis of cancer

oncogenes, tumor suppressor genes, apoptosis genes, DNA repair genes

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Oncogenes

growth factors, growth factor receptors, signal transduction proteins, nuclear regulatory proteins, cell cycle regulators

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Growth factors

sis, hst-1, int-2

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GF sis

PDGF overexpression

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GF hst-1

FGF overexpression

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GF int-2

FGF amplification

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Growth factor receptors

erb-B1-3, fms

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GF-rec erb-B1-3

EGF Truncation

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GF-rec fms

CSF-1 point mutation

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Signal transduction protein

ras, abl

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ST ras

GTP-protein point mutation

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ST abl

tyrosine kinase translocation

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nuclear regulatory protein

myc, L-myc, N-myc, fos, jun

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NucReg myc and APC casset

transcription, changed by translocation/amplification

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cell cycle regulation

Cyclin D, CDK4

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CellCycle Cyclin D

Cyclin, translocation/amplification

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CellCycle CDK4

CD kinase, amplification/point muation

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how CDK and Cyclins work together

CDK is always present, cyclin is synthesized to activate CDK

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major cyclins in G1-S

D and E

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major CDK in G1 to S

2, 4, 6

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inhibitors of CDK 4 and 6

p21, 27, 57, 26-19

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action of activated CDK 2, 4, 6

phosphorylates Rb which releases E2F family of transcription factors, allowing cell to proceed from G1 to S

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Cyclin D binds

CDK 4/6 for G1 to S passage

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Cyclin E binds

CDK 2 for G1 to S passage

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Cyclin A binds

CDK 2/1 for S to G2 passage

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Cyclin B finds

CDK 1 for passage from G2 to M

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CDK4 inhibitors

p 15, 16, 18, 19

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CDK 6,2,1 inhibitors

p 21, 27, 57

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CIP/KIP family CDK inhibitors

p27, p16

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p21 is induced by

p53

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p27 is induced by

TGFbeta and other suppressors

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INK4/ARF family CDP inhibitors

p16, p14

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p16 inhibits by

binding cylinD-CDK4 promoting Rb inhibition

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p14 inhibits by

increasing p53 by inhibiting MDM2

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p53

tumor suppressor, causes cell cycle arrest and apoptosis by inducing p21 and BAX; inhibited by MDM2