cancer and apotosis

death cues

extracellular signals that are going to tell cells to dia via apoptosis or necrosis

what different cues are in cells

death cues, survival cues, proliferating cues, and growth inhibition cues

whats the difference between a normal cell and a cancer cell

normal cell when given these cues will either lead to cell death or stop cell division but in cancer cells they transform into a different phenotype where they ignore death and growth inhibition cues and produce their own survival and proliferation cues leading to sort of immortal cells that cause tumors because they divide to many times

BRAC1 mutation

leads to breast or prostate cancer (does not mean going to get it but increases chances)

p53

very important transcription factor that blocks cells from diving

RB1

gene called retimoblastoma 

familial cancers

only make up 5-10% of cancers

sporadic cancers

due to environmental conditions and take a long time

importance of G1/S checkpoint 

cells have divides and now been exposed to all sorts of things so right before they replicate need to fix mutations in the DNA if there are so it doesn’t not get carried through replication and become a permanent mutation 

G2/M checkpoint

stops the cell from going into mitosis so it stops at G2

how are tumors classified

tissue of origin

how do tumors begin

by cells continuously proliferating which start as a benign tumor that is not a problem until it is located somewhere dangerous

what are the different genes that may be mutated

signal genes, proliferating genes, and cell cycle checkpoint genes

singal gene

kinases can be mutated to form tumors they produce proteins that take a signal from the outside and the signal transduction across the membrane

proliferation genes 

these are the cyclins that drive the cell cycle if they are mutated they can cause cells to proliferate uncontrollably like cyclin D will hyperphosphorylate and release RB and E2F because CKI is not able to bind

cell cycle checkpoint genes

the p21,p53, etc and a lot of mutations of these cause cancers

oncogenes

mutant alleles that act dominantly to promoter proliferation, can be heterozygous for the condition. if there is one mutant and one wild type of the cyclin or CDK then will still drive cells through the cell cycle and make them proliferate uncontrollably

proto-oncogene

non-mutant prescursor to oncogenes ( before they are mutated)

mutant tumor-supressor genes

mutatant alleles that are recessive, both copies must be mutant to make the cells abnormal. As long as you have one wild type of CKI they can continue to stop the cell from cyling

The RAS

one of those kinases that start signaling early usually activated by tyrosine kinases. when its inactive does not do anyhting but when active it gets phosphorylated and phosphorylated a downstream kinases so continuous activation until not needed and goes back to a GDP

what happens if RAS becomes an oncogene 

once it becomes activated will cannot be able to turn off and lead to proliferation of cells leading to tumor formation 

cyclin K

cyclin can act for any other cyclin and can get it from any virus but cannot be stopped by CKIs and automatically starts tumors

what 2 oncogenes does HPV(human papilloma virus carry

E6 causing degradation of p53 and E7 which binds and activated Rb

how can proto-oncogenes become activated

amplification, point mutation, and translocation 

what must maligant tumor must acquire

independence from external growth siganls, insensitivity to anti-growth singals, avoidance of apoptosis, capability to proliferate indefinitely, sustained angiogenesis, and invade tissues, and metastasis

how does retroviruses cause cancer

the RNA is reverse-transcrived into DNA and it’ll be incorporated into the host genome leading to producing a lot of cyclins

apoptosis 

a programmed, controlled process by which a cell actively triggers its own dealth usually to remove damaged, unwanted, or dangerous cells in a multicellular organism

membrane blebbing

DNA and membrane is going to be condensed down and chopped up 

caspase-dependent apoptosis (cysteine-aspartic protease)

zymogens (inactive), initiator are activated forming complexes (apoptosme) which are cleaved activating effector/executioner caspases done by 2 ways intrinsic and extrinsic

initiator 2,8,9,10

capsases that will do the cleavage of the executionar caspases

effector 3,6,7 (executioner)

initiator caspases activate effector caspases, once cleaved can cause problems in the apoptosis of the cell

intrinsic pathway

removal of NGF or cellular stress getting an intracellular signaling, transcription factors are activated which turn on a subset of genes (Bax, Bcl-2, BID-tBid), leading to mitochonrdia dysfunction, cyctochrome C is released forming apoptosome with Apaf-1, caspase 9 activates caspase 3 leading to activation of effector caspases

in intrinsic pathway what do the subset genes (Bax, Bcl-2, and Bid) do

cause the membrane issues in mitochondria releasing cytochrome C

what is the difference between intrinsic pathway and extrinsic pathway

intrinsic required new protein syntehsis which takes longer while extrinsic does not require that or mitochonrial dysfunction so takes less time

extrinsic pathway

death ligan binds to death receptor which turns on small intracellular signalining event leading to caspase 8 activation that activates caspase 3, and activating effector caspase 

caspases-independent apoptosis

Apoptosis-inducing factor(AIF) a mitochondrial protein involved in respiration and redox reactions on x chromosome that begins to function improperly triggering chromtain condensation and DNA degradtion

intracellular singaling

lignad released by one cell binds to specific receptor on another cell triggering intracellular signaling in receptor cell through endocrine or paracrine

endocrine

use of hormones as long-range singal molecules through circulator system (small molecules) for regions that go through lymphatic system or circulatory system

paracrine

short range protein ligand that dont use circulatory system just locally

what does intercellular signaling lead to

different populations of cell

protein ligands and transmembrane receptor

protein ligants act as signals by binding to transmembrane receptors on cells, the receptors must have extracellular domain (binds ligand), transmembrane domain (ausually hydrophobic AA), and intracellular/cytoplasmic domain (passes signal inside). cann have many transmembrane regions

how the signal is transferred inside the cell

GF gonna come in and bind to a receptor tyrosine kinase(RTK), which phosphorylate each other (homodimer), recruits an adapter protein when they become phosphorylated recruit it in a system (RAS) which is bound to GTP and activated and GDP when inactivated

opistocones

a big split between the gene famoles get the ERK family members