81 terms

Cell Bio Cancer

undergoes V to Q substitution to generate Neu oncogene
EGF receptor
gene deletion to generate ErbB oncogene
blocks EGF binding to HER2, increases HER2 endocytosis
GEF for Ras, exchanges GDP for GTP to activate
GAP for Ras, increases GTPase activity of Ras to deactivate
activates Raf, can be mutated to be constitutively active oncogene by altering G12 or Q61 to X
activated by Ras through dimerization, mutated oncogene works as monomer
inhibits mutant B-Raf, but truncated variant of mutant B-Raf has evolved resistance to vemurafenib
fusion oncokinase created by translocation of Abl gene from 9 to 22 chromosome, causes CML
binds to active site of Bcr-Abl to prevent substrate binding.1st drug targeting a tumor-specific kinase
Binds to EGF receptor; however binds to many other kinases since they are similar in structure.
produces transcription factor Myc, which regulates genes involved in cell growth. can be activated by mutagenesis, retroviral insertion, or translocations of chromosomes.
can integrate next to c-myc gene and elevate transcription. Requires chronic viral infection
Cyclin D
Ultimate target of RTK signaling. activates CDK4. Phosphorylates Rb which dissociates from E2F
binds to CycD/CDK4 complex to inhibit it. can be swamped by excess CycD
Tumor surpressor gene that inhibits E2F, dissociates when phosphorylated
activator of transcription of proteins needed for DNA synthesis.
Oncoprotein that binds Rb and prevents it from binding to E2F, resulting in E2F passing freely through R point.
The Ames Test
Demonstrated carcinogens are mutagens by selective for a rare mutation unable to grow without histidine. Observe for mutation that allows them to grow without histidine.
Direct acting carcinogen
mutates DNA without metabolic activation by liver enzymes
Indirect acting carcinogen(procarcinogen)
mutate DNA after converted metabolically to ultimate carcinogens
an indirect carcinogen that modifies G to pair with A instead of C. If left unrepaired, converts G to T, causing loss of function in p53
indirect carcinogen in hotdogs, oxidation by P-450 in liver turns it into a mutagen.
Aflatoxin B
indirect carcinogen on mold in peanuts.
intra-S phase checkpoint. inhibits cdc25C preventing cyclin-CDK to begin mitosis
APC target: spindle-assembly checkpoint. inhibit cdc20 preventing activation of separase and anaphase.
APC target: spindle-position checkpoint. prevents cdc14 activation and degradation of mitotic cyclins
DNA-damage checkpoint. inhibits cdc25A preventing entry to S phase.
tumor surpressor gene that activates checkpoints at various points in cell cycle. At low concentration, targets growth arrest genes. At medium concentration, targets DNA repair genes. At high concentration, targets Apoptosis regulating genes.
Kinase that stabilizes p53 and inactivates Mdm2 through phosphorylation
phosphorylated by ATM, phosphorylates Cdc25A to deactivate it
ubiquitin ligase that degrades p53, is deactivated by ATM resulting in an increase of p53 protein. also deactivated by pArf14
individual cell programmed suicide. results in bodies consumed by neighboring cells. can be caused by genome damage or other unfixable problems in cell. DNA is cleaved at specific sites
cell murder, caused by absence of nutrients, changes in temperature, external stress. DNA is randomly cleaved
cleaves DNA into 200 bp fragments which are degraded
Part of the apoptosis pathway, activated by Cytochrome C and p53. Activates Caspase-9
Part of the apoptosis pathway, activated by Apaf-1 and p53. Activates Caspase 3,7
Cytochrome C w/dATP
starts the caspase cascade when it is released from the mitochondria, activates Apaf-1
Part of the apoptosis pathway, targets cellular signals that cause apoptosis, activated by Caspase-9
inhibits the release of Cytochrome C and dATP conversion. Is inhibited by p53.
inhibits activation of Caspase 3,7 and of its targets
p53 mutations
eliminate DNA binding and destabilize the protein. Only requires one p53 subunit to eliminate function in a p53 tetramer. mostly missense spots.
viral protein that targets p53, acting as a ubiquitin ligase
becoming homozygous for the recessive loss-of-function gene in tumor surpressors. occurs by mis-segregation of alleles in mitosis or mitotic recombination
When cell goes into Go indefinitely, associated with aging. Occurs after about 50 cell cycle generations because of telomere loss
Clonal expansion
expansion of cancer stem cells that occurs with an oncogenic mutation. each successive expansion occurs when another mutation occurs.
Hallmarks (phenotypes)
specific physical properties of cancer cells that are caused by various oncogenic genetic mutations.
stimulates oocytes arrested in G2 to begin meiosis. example of an MPF
CDKs (Cyclin Dependent Kinases)
drive the cell cycle, regulated by synthesis and degradation of cyclin subunit, and phosphorylation of catalytic CDK unit
cdc mutant
arrests cell at a certain point in cell cycle when mutated, generates string like cells
MPF(maturation/mitosis promoting factor)
Drives oocytes from G2 arrest to M, aka cyclin/CDK complex
Cyclin D/E
G1/S cyclins that work with CDK to drive the cell cycle
Cyclin A/B
G2/M cyclins that complex with CDK to drive the cell cycle to M (A is also an S cyclin)
APC(Anaphase promoting complex)
ubiquitinates cyclins, is phosphorylated/activated by cyclin/CDK
indirectly inhibited by MPF. when MPF is degraded, PP2-B55 dephosphorylates MPF. Always opposite to MPF in concentration
wee mutant
causes a small cell phenotype representing decreased G2 time. the Normal wee1 inhibits Cyclin/CDK(MPF) to delay entry to M.
CAK (cdc-activating Kinase)
phosphorylates MPF, is activated when ribosomes have doubled in number, aka cell has doubled in mass
Lamin B
forms mesh like tetramers and filaments to form nuclear membrane. phosphorylated by MPF to be depolymerized
phosphorylated by MPF and packs chromatin into chromosomes
Histone H1
phosphorylated by MPF and packs nucleosomes
Pericentrin Gene
loss of function mutations in this gene cause Dwarfism
+ end stabilizing protein that is inactivated by MPF phosphorylation
non-coding DNA sequence with a structural function, not informational
inhibits separase, degraded by APC in order to allow sister chromatid to separate
cleaves Kleisin to release cohesins that hold the sister chromatids together
Mitotic Spindle Checkpoint (MSC)
prevents activation of APC, MAD1/MAD2 inhibit activation of APC until all kinetochores are captured
Aurora B Kinase
activates the spindle checkpoint, opposite to protein phosphatase 1
Phosphatase 1
turns off spindle checkpoint
Anaphase A
Kinetochore MTs depolymerize at both ends separating the chromosomes
Anaphase B
Poles move further apart by dyneins pulling the astral MTs apart and kinesins pushing the polar MTs apart.
inhibits depolymerization of MTs, therefore inhibiting Anaphase A
inhibits polar MT polymerization, therefore inhibiting Anaphase B
Midbody Remnants
Left over remnants after cytokinesis from the mid region of the two cells. If left in cell, it remains pluripotent (stem cell). If absent from cell, differentiation occurs
requires actin/myosin. Karyomeres fuse to form nucleus, contractile ring forms and contracts to split cells
Free HER1
HEGF receptor not bound to any EGF. endocytosed much slower from cell than the active dimer form.
protein binds to active phosphorylated HER1, SH3 subunit then binds SOS that activates Ras
inhibitor of Raf, binds and inactivates it when Raf is phosphorylated by MAPK
dual specificity kinase activated by Raf, activates MAPK
T,Y kinase activated MEK after phosphorylation. Activates p90rsk and TCF
phosphorylates SRF that binds to SRE which codes transcription for c-fos, jun, c-myc which activate Cyclin D expression
activated by MAPK and also binds to SRE which codes transcription for c-fos, jun, c-myc which activate Cyclin D expression