signaling and cell cycle control

G0 phase

phase where cells are not growing or dividing

G1 phase

phase where cells are getting ready for replication

quiescent phase

known as the temporary G0 phase. differentiated cells stop dividing and enter this phase.

peptide

________ hormones are hydrophilic and cannot cross the membrane.

cell-surface; intracellular

peptide hormones require a receptor, so they bind to __________ receptors like RTKs to activate __________ signaling pathways.

steroid

_________ hormones are hydrophobic and can cross the membrane.

nuclear hormone; secondary messenger

steroid hormones bind ___________ receptors. those receptors are transcription factors, so no need for a _______________.

• altered gene expression

• increased translation

• increased nutrient uptake and metabolic rate

• altered morphology (duplicating genome requires cell to be a lot bigger)

cells growing to divide experience:

dimerization

estrogen binding induces estrogen receptor (ER) ___________

estrogen response element

estrogen binds to genes containing an…

coactivator

estrogen receptor interacts with a _________ to activate transcription. this opens up chromatin and recruits things like HATs to acetylate histones

tamoxifen

estrogen antagonist that competes with estrogen for binding to the ER

it prevents the ER from recruiting coactivators so transcription does not get activated

how does tamoxifen work?

IGF-1

_______ activates the Ras pathway via RTK

autophosphorylation

peptide binding to RTKs stimulates ________

GRB2

_______ binds to phosphorylated RTK

SOS; Ras

GRB2 recruits _____, which activates ______

Ras-GDP

the inactive state of Ras

Ras-GTP

the active state of Ras

GTPase activating protein

controls Ras signaling. tells Ras to hydrolyze GTP

Ras-GTP interacts with _____, activating its kinase activity

RAF

MEK

Raf phosphorylates _____

ERK

MEK phosphorylates ______

transcription factors

ERK phosphorylates ___________ in the nucleus

ELK-1

______ binds the serum response element located in pro-growth genes to activate their transcription

signaling cascade

signal amplification due to sequential activation of protein kinases

protein phosphatases

remove phosphates from the proteins. this shuts down the signal

FOS

ELK-1 binds SRE in the promoters of many pro-growth genes, one of which is _______

JUN; AP-1

FOS dimerizes with _____ to form the _____ transcription factor complex

Mad/Max

____/______ is the repressor of pro growth genes. it recruits HDAC, blocking transcription

Myc/Max

_____/_______ is the activator of many pro growth genes

they are not growing or dividing. they only produce it when needed.

why do most cells not produce Myc?

cyclin D

upregulation of ________ by AP-1 and Myc officially signals we are in the G1 phase

catalytic; regulatory

each active kinase has a ______ subunit and a _______ subunit

CDKs

catalytic subunits are _______

cyclins

regulatory subunits are ______

• CDK phosphorylation or dephosphorylation

• ubiquitin degradation

• CDK inhibiting proteins (CIP)

cyclin-cdk activity depends on:

cyclin D- CDK 4-6

this cyclin-cdk complex controls the early g1 phase and initiates transition toward the restriction point

cyclin E- CDK 2

this cyclin-cdk complex is responsible for the hyperphosphorylation of Rb, and activating S-phase

cyclin A- CDK2

this cyclin-cdk complex is needed to sustain S phase and helps initiate replication. it is activated by cyclin E- CDK2

restriction point

checkpoint before DNA replication

committed

passing the restriction point in G1 means the cell is now ________

CDK inhibitors

___________ make up the restriction point

inhibitor of cdk4

proteins that bind to CDK 4/6 blocking cyclin D binding

CDK interacting protein

binds to and inhibits the activity of intact CDK-cyclin complexes

retinoblastoma protein

corepressor that binds the activator E2F to arrest cell division

cyclin d cdk 4/6 and cyclin e cdk 2

which two cyclin cdk complexes hyper phosphorylate Rb, releasing it from E2F

E2F

______ help activate transcription of genes required for S phase entry. it is a transcriptional activator of cyclin A

p53

if DNA damage is present, _____ activates transcription of CKI genes, such as p21. this blocks CDK from binding ATP.

it triggers the activation of p21, which prevents the phosphorylation of Rb so that the cell is arrested at the G1/S checkpoint. it also activates repair genes and if the damage is bad enough, senescence or apoptosis is activated.

how does p53 work?

A

transition to the S phase requires synthesis of cyclin ___

sic1

____ inhibits cyclin A- cdk2

phosphorylates

cyclin e cdk2 _______ sic 1, making it inactive

ubiquitin ligase

phosphorylation of Sic1 makes it susceptible to a ___________

guanine nucleotide exchange factor

SOS is a ______________