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Bcr Abl

in frame fusion protein between chromosome 9 & 22

causes leukemia, treated wit Gleevec

Rb

many signaling pathways converge to regulate phosphorylation of this protein, which controls the R point

tumour suppressor that causes retinoblastoma

driver mutations

cause expansion of unique subpopulations

R point

between G1 & S, decision to divide

convergence of many growth and inhibition pathways

cyclins

form complexes with Cdks to promote/regulate events of the cell cycle

cyclin dependent kinases CDKs

enzyme that regulates cell cycle progression and is activated by cyclin proteins

E2F

transcription factor that prevents transcription of Rb

bound when Rb is hy**po**phosphorylated

when released, drives transcription of cyclins

activates genes involved in progression from G1 to S phase

p53

tumor suppressor responsible for cell cycle arrest, DNA repair, block of angiogenesis (blood vessel growth) and apoptosis

tetramer

MDM2

ubiquitylates p53 for degradation

Scr

inhibited when bound to tyrosine 527

activated when tyrosine 416 is phosphorylated

non-receptor tyrosine kinase

v Scr

viral oncogene caused by rous sarcoma virus (RSV)

causes increase in tyrosine phosphorylation

western blot

detect specific proteins using specific antibodies

receptor tyrosine kinase RTK

respond to growth factors

enzyme coupled receptor, forms a dimer after ligand binding

Src and Kras are intracellular response to GF binding to receptor

have intracellular tyrosine kinase domains and variable extracellular domains

epidermal growth factor receptor EGFR

transmembrane protein that is activated by dimerization upon growth factor binding                       

RTK that has cytoplasmic tyrosine kinase domain homologous to Src

non receptor tyrosine kinase

do not have receptor activity but interact with proteins that do

ex - Src

GPCR

respond to GEFs by activating G proteins (large heterodimers)

7 helical transmembrane domains

large scaffold proteins

assemble groups of multiple downstream signaling components

PI3K

activates downstream of growth factor signal

converts PIP2 to PIP3

PIP3 recruits Atk which influences proliferation

PTEN

converts PIP3 to PIP2, inhibiting Akt and stopping cell proliferation

Loss (deletion/mutation) of this phosphatase increases Akt signaling in cancers

Ras

activated by GEF

stimulates pathways that promote tumour development and progression

MAPK

scaffold protein-mediated signaling cascade that promotes proliferation and is activated downstream of Ras

second messenger

influence activation/inhibition of proteins/pathways

generate in large amounts in response to signal activation to amplify that signal

ex - calcium ions

Ku protein

ring shaped heterodimer protein used in nonhomologous end joining to fix double strand breaks

Akt

serine/threonine kinase that binds to PIP3

activation involves binding to a phosphoinositide

sporadic

cancers that are initiated by mutations in somatic cells that are not found in the germline

Li-Fraumeni syndrome

condition caused by inheriting a p53 mutation

phosphoinoditides

phosphorylated lipids in cell membranes, regulating signaling, membrane trafficking, and cellular processes.

ex - PIP2, PIP3

anoikis

cell death when detached from extracellular matrix

endocrine

signaling factors that travel long distances in blood

paracrine

signaling involves secreted factors with a limited range (signal within a localized region)

juxtracrine

signaling is mediated by contact diffusible factors

autocrine

cell producing the signal is the same type as the cell receiving the signal

GAPs

promote GTP hydrolysis

GEFs

stimulate release of GDP so GTP can bind

iPSCs

pluripotent cells derived from the somatic cells of a patient's own body

master regulator

transcription factor with a key role in directing cell fate

lncRNA 

have regulatory roles, usually to decrease gene expression

RNA molecules that can act in cis or trans to influence transcription

2D gel electrophoresis

separates proteins by mass and charge to create an array of dots that reflect the proteome of the cell type analyzed

in situ hybridization

uses an RNA probe to identify where a particular mRNA is expressed

heatmap

uses different colors to indicate high and low expression to display gene expression data

reporter gene assay

to characterize the effects of any enhancers that could be present in a segment of DNA, that sequence of DNA is fused to a green florescent protein (GFP) gene

ChIP-Seq

can be used to identify the DNA sequences that a particular insulator protein binds to

RNA-Seq

can be used to discover which RNA are expressed in a particular cell type

transcriptome

complete set of RNA molecules present in a cell, tissue, or organism at a specific point in time

cis regulatory elements

regulatory DNA sequences located adjacent to gene they regulate

generally sequences encoded on the same chromosome as the gene they affect

ex - promoters, enhancers, silencers

trans regulatory elements

bind to cis elements, can regulate multiple genes and can be expressed from any chromosome

ex - transcription factors, microRNA

activators

bind to enhancer DNA elements

cause change to chromatin structure

repressors

bind to silence DNA elements

insulators

alter 3D arrangement of chromatin to divide DNA into looped regions

operon

polycistronic cluster of genes that share a cis-regulatory element

in prokaryotes

operator

cis regulatory element that words on a polycistronic cluster of genes

tryptophan repressor

binds to operator when tryptophan is present to inhibit further transcription

lac repressor

binds when there is enough glucose, enough energy, or no lactose in the bacteria

releases when there is low energy (cAMP) and high lactose

negative splicing control

prevents access to splice site

positive splicing control

directs splicing machinery to splice site that would otherwise not be used

exon junction complexes EJC

mark a complete splice

RNA editing

post transcription modification that changes base pairs

adenosine can become inosine (A→I)

cytosine can become uracil (C→U)

5’UTR

capping region of mature mRNA that does not encode for proteins

3’UTR

polyA and cleavage region of mature mRNA that does not encode for proteins

untranslated regions UTRs

mRNA stability (how long mRNA is present)

mRNA translation (when, how often)

mRNA localization (where in cell)

endonuclease site

when exposed, allows for mRNA degradation

found at 3’UTR

maternal contributions

proteins and RNA that are stored in the egg until they are needed to orchestrate early development

Xist

lncRNA that triggers X-inactivation

RNA interference RNAi

small non-coding RNA recognize targets by complementary base-pairing and regulate a large number of eukaryotic genes

ex - siRNA, piRNA, & miRNA

miRNA

hairpin after transcription

target RISC complex to particular mRNA based on complementary pairing

cleaved in nucleus and cytoplasm

siRNA

double stranded RNA from endogenous source

transfected into cells to knockdown expression of target mRNA

argonaute protein

associated with RISC complex

RISC complex

RNA-Induced Silencing Complex

associated with Argonaute proteins

guides the small RNAs to target mRNAs resulting in degradation or repression

Clustered Regularly Interspaced Short Palindromic Repeats

CRISPR

use a gene-specific guide RNA sequence to direct the Cas9 nuclease to a specific site

p bodies

\
membrane-less regions of the cytoplasm where RNA can accumulate

snRNA

removes lariant from pre-mRNA, forms spliceosome

ex - U1, U2, U4, U5, U6

snoRNA

small nucle__o__lar RNAs

modify rRNAs

spliceosome

large assembly of RNA and protein molecules (snRNPs) that performs pre-mRNA splicing in eukaryotic cells

ribozyme

release factors

bind to vacant A site and catalyze addition of water instead of amino acid to free the C-terminus to end translation

EF-Tu

helps with checking accuracy of codon/anti-codon interaction

eIF4G 

connects the 5' cap and 3' polyA tail of the mRNA to create a circular message in eukaryotic translation initiation

20

there are # different amino acids

shine dalgarno sequence

in prokaryotes

complementary to sequence near 3’ end of 16S rRNA

positions small ribosomal subunit in the correct spot

IF1

helps with attachment to mRNA

translation initiation in prokaryotes

IF2

GTP-binding protein that is required for attachment of first AA-tRNA

translation initiation in prokaryotes

IF3

prevents premature attachment of large subunit

translation initiation in prokaryotes

eIF4E

binds to 5’ cap of mRNA in eukaryotic translation initiation

Kozak sequence

small ribosomal subunit along with eIFs and initiator tRNA finds 5’ end of mRNA and scans along until reaches a _________ ___________

constitutive expression

protein present in all cells all the time

ex - beta actin

U1

binds to 5’ splice site

in splicing

snRNP

snRNA complex with proteins that form the spliceosome

U2

binds the branch point site causing adenosine to budge out

in splicing

U6

replaces U1 at the 5’ splice site

pairs with U4 originally

cryptic site

exon skipping due to similarity to a splice site consensus sequence

RNA exosome

degrade RNA in the nucleus unless proteins are bound

nucleoli

ribosomal DNA clusters that come together during interphase

s value

Svedberg unit

measure of the sedimentation rate during centrifugation affected by both mass and shape

the larger the molecule, the larger the S value, the faster the sedimentation

40S

s value for small ribosomal subunit

60S

s value for large ribosomal subunit

rho factor

bacterial protein for transcription termination

RNA pol I

transcribes 5.8S, 18S, and 28S rRNA genes

RNA pol II

transcribes all protein coding genes, snoRNA genes, miRNA genes, siRNA genes, licRNA genes, and most snRNA genes

RNA pol III

transcribes tRNA genes, 5S rRNA genes, some snRNA genes, and other small RNAs

TFIID

recognizes and binds the TATA box