Cancer Biology Exam 2

immediate early genes

genes switched on within 30 minutes of GF stimulation. Activated by preexisting transcription factors turned on via phosphorylation, do not require new protein synthesis

delayed early genes

genes expressed later (~60 min) activated by transcription factors made by IEGs mRNA, require protein synthesis

bridging/adapter protein

proteins with no enzymatic activity of their own link an activated receptor to downsteam signalling proteins

SH2

bridges phosphorylated tyrosines

SH3

bridges proline-rich sequences. binds SOS RAS GDP exchange factor

RAS effectors

proteins that bind active RAS to GTP and pass signal on

Phosphotase

enzyme removes phosphate groups, opposes kinases, shuts signals off.

anoikis

initation of apoptosis when cells cannot live without attachment to ECM

interphase

G1 + S + G2 period b/w mitosis then cell growth + replicated DNA

G0

non dividing state → center reenter cell cycle or ar terminally differentiated

cell cycle checkpoints

halt cell cycle if deficiencies are detected (DNA damage, incomplete replicaiton, cell size, spindle attachment)

pRb

tumor suppressor → governor of R point by blocking E2Fs + G1→ S transition

cyclins

regulator proteins → levels fluctuate to regulate CDKs

CDKs

ser/thr kinases → only active when bound to cyclin, at constant levels

E2Fs

transcription factors turn on genes for S phase

R-point

Late in G1 → decision for cell to move forward or not → must commit to cycle after, influced by growth factors, TGF-B, nutrients, cell size, DNA damage

G1

cell is responsive to mitogenic growth factors and TGF-B

ligand independent

receptor signaling w/o having a ligand bound, occurs via receptor over expression/point mutation

constitutively active

always on regardless of signals present, signals continuously not just in presence of ligand

endocrine

signal secreted from far away in the blood stream

autocrine

GF released by cell undergoing signal transduction → self secretion

paracrine

GF released by neighboring cells when signal transduction takes place in target cell

tyrosine kinase

phosphorylates tyrosine via ATP activates/inactivates certain proteins

p53

“guardian of genome” homotetrameric tumor suppressor gene, leads to cell cycle arrest, apoptosis, senesence

intrinsic apoptosis

internal signals (DNA damage/cell death) cause cytochrome c release from mitochonria, activates caspace 9 leading to programmed cell death via effector/executioner caspace 3

extrinsic apoptosis

extracellular death ligand binds to a death receptor activating initiator caspace 8 leading to programmed cell death via effector/executioner caspace 3

initator caspase (8,9,10)

inactive soluble monomers, activated by dimerization and cleavage → cleave and activate executioner caspases

executioner caspase (3,6,7)

inactive dimers inactivated by initiator cleavage, cleave death substrates

dominant negative mutation

mutant subunit poisons wild type subunit, function of whole complex is lost even though allele is present

senescence

cell stops dividing, does not enter the cell cycle, still metabolically active, not dead

necrosis

wide spread non programmed cell death when cells swell and lyse causing inflammation