Term
|
Definition
Telomeres form T-loops to prevent p-53
mediated repair of dsDNA breaks
Ribonucleoprotin caps ends of chromosomes |
|
|
Term
|
Definition
TERC: RNA template
TERT: Reverse transcriptase
Extends 3' end. DNA pol elongates 5'end
Up regulation of MYC(upregulates telomerase) |
|
|
Term
|
Definition
1mutated telomerase allele
Prematurely shortened telomeres
progressive bone marrow failure
epidermal structure abnormalities |
|
|
Term
|
Definition
Triggers cellular senescence(G0)
or cell cycle arrest in G1
DNA damage activates p53. |
|
|
Term
|
Definition
PLC breaks down inositol to IP3 and DAG
IP3 causes calcium release.
Ca + DAG activate PKC.
PKC activates TFs |
|
|
Term
|
Definition
Pl3K phosphorylates membrane lipid,
activates PKB/AKT.
PBK/AKT -> BCL-2.
BCL-2 prevents pore formation in mitochondria. |
|
|
Term
|
Definition
GRB2 -> SOS(Ras GEF)
SOS -> Ras -> MAPK
Production of TFs, GFs. cell cycle proteins.
Cell proliferation and growth.
MAPK activates expresion of genes required for progression through cell cycle. |
|
|
Term
| HER(Human epidermal GFR, EGFR) |
|
Definition
EFF receptor(Erb/Her)
HER2/EGFR amplified in breast cancers
Herceptin is antibody against HEr 2 to treat breast cancer
Humanised mAB, Trastuzumab(herceptin) block HER2 signalling |
|
|
Term
|
Definition
Small molecule kinase inhibitors.
Block tyrosine kinase activity |
|
|
Term
|
Definition
LOF in Ras-GAP(NF1 neurofibronin)
AD genetic disorder
Tumors grow along peripheral nerves and skin
Ras must also be directed to the membrane by farnesyl group. (Farnesyl transferase) |
|
|
Term
| Steroid Hormones and Cancer |
|
Definition
Estrogen/estradiol enhances
transcription of cyclin D.
Tamoxifen binds to same site as
estradiol(down regulates cyclin D)
Androgen receptor antagonists:
therepeutic target for prostate \
cancers.
PSA is a marker for prostate cancer
Flutamide, bicalutamide: androgen
receptor antagonists |
|
|
Term
|
Definition
Interphase:Chromosome duplication
Prophase: Breakdown microtubles,chrosome
Condensation
Metaphase:Nuclear envelope dissolves
Chromosomes align metaphase plate
Anaphase: chromosome move to poles
Telophase:Nuclear evenlope reassembly
formation of contractile ring
Cytokinesis:reformation ofmicrotubules,
contractile ring separates cells |
|
|
Term
|
Definition
Cyclins regulate CDK activity.
Change during cell cycle. Fluctuation
regulated by ubiquitin ligase targeting
CDKs: phosphorylate regulatory proteins
CDK level usually constant. |
|
|
Term
|
Definition
Cyclin D binds CDK4,6.Required for for G1 restriction point
Cyclin E binds and activates CDK2
G1-> S transition
DNA damage pathways target degradation of cyclin D 1st |
|
|
Term
|
Definition
p16INK 4: inhibit cyclin D-Cdk4/6 complex
CIP: inhibit CDK complexes. P21. |
|
|
Term
| Negative regulation by TGF-B |
|
Definition
TGF-B modulates levels of CDK-inhibitors
Mostly P15, weakly p21. Dna damage
stimulates p21
Phosphorylates SMad2/3 binds Smad 4.
Smad 4(TF) increases p15,16
TGF-B prevents phosphorylation of pRBby
producing inhibitors of CDK4,6 complex. |
|
|
Term
| Li-fraumeni Syndrome(LFS) |
|
Definition
Increased risk for developing multiple primary cancers.
Mutation in p53. Inhibits cell cycle
via p21(inhibits Cdk complex)
p53 DNA repair enzymes via GADD45
p53 Apoptosis via Fas and BAX
ATM phosphorylates p53 |
|
|
Term
|
Definition
p53 levels kept low by MDM2.
MDM2 binds and ubiquinates
hypophosphorylated p53. degrades
Excess MDM2 prevents p53 from acting as
a checkpoint.
p14ARF sequester MDM2.Increase in p53.
High levels of Myc cause synthesis of
ARF via E2F |
|
|
Term
|
Definition
Cyclin B + CDk1(MPF)is major complex
causing progression
CAK activates MPF(adds on phosphate)
Wee1 inhibits MPF(adds a phosphate)
Phosphatase Cdc25 removes wee1
phosphate
M-CDK complex leads to nuclear envelope breakdown. Phosphorylates Lamins.
Chromosome condensation spindle assembly
Cyclin B synthesis starts in Sphase |
|
|
Term
Anaphase Promoting Complex(APC)
And
Mad2 |
|
Definition
APC/C initiates sister chromatid
Seperation.Degrades all cyclins
MAd2 is kinetochore sensor. binds to unattached kinetochores.
Inhibits APC/C activation.
Blocks metaphase-anaphase transition |
|
|
