8L11 Growth Factor and Cell Cycle

quiescent

G0 temporary

(senescence is permanent)

cyclin-CDK

2 subunits, CDK = catalytic unit (1 2 4 6) activated with cyclin but always lowly expressed

cyclin = regulatory unit (A B D E)

cyclin-cdk oscillations

CDK Plation/DPlation

controlled cyclin degradatino

synthesis of CDKs and cyclins

action of CDK inhibiting proteins

cdk regulation by Plation and proteolysis

cyclin Plated ATP bind site make inactive,

ubiquitin = triggers proteolysis

proteasomes = proteolytic enzyme complexes, degrades cyclin leaving CDK inactive

DBRP = adds ubiquitin to cyclin

DBRP

destruction box recognizing protein

growth factors

EC signals, Plate and start cell cycle with nuclear TFs

AP1

TF vital in cell cycle

Jun + Fos

E2F

needed to enter S phase, activates DNA synthesis enzymes and active kinase complexes

cell cycle inhibitors

normal,

example p21

estrogen receptor ER

nuclear hormone receptor,

line mammary epithelial

estrogen binds to receptors and promotes growth and division

1. inactive monomer,

2. cross into cell,

3. binds receptor > dimer,

4. enters nucleus,

5. binds zinc finger domain

6. recruits coactivators and transcription amchinery

Jun gene

one half of AP1, made by estrogen receptor

tamoxifen

estrogen antagonist competes for binding to ER

RTK

receptor tyrosine kinase;

in plasma membrane, receptor dimerizes and Plates its own tyrosines to help bind pathway activators via signal transduction

RAS

peptide binds RTK, autoP

GRB2 binds tyrP, SOS binds GRB2 as GEF (guanine nucleotide exchange factor)

SOS targets Ras-GTP > Ras-GDP

Ras signaling off by GTPase activating protein (GAP)

Ras-GTP activates RAF kinase activity, MEK, ERK, ELK1, SRE, FOS

protein phosphatases

Plation and activity of target proteins reversed by

AP1

Jun + Fos, leucine-zipper factor

transcriptional activator

binds TRE cis-acting element

regulates many genes for cell cycle

cyclin D

AP1 and MYC stimulates production in G1 phase

MYC

HAT for pro-growth genes

restriction point

checkpoint before DNA replication

MAD/MAX

repressor of pro-growth genes,

MYC/MAX

activator that promotes transcription of pro=growth genes

recruits histone deacetylases