Wee1 Myt1 p27Kip

p21 Cip

Cyclin D1

GSK-3

glycogensynthase

Tpl2

IKK

eNOS

Huntingtin

Ataxin-1

GABA A

AS160

PFKB2

PIP5K

PDK1

paxi

llin

FAK

ILKPI

3K

PI3K

PTEN

RTKIntegrin

Gab1

Gab2

IRS1

Raptor

S6

p70 S6K

PDCD4GßL

mTOR

XIAP

TSC2TSC1

PDCD4

FoxO1

Bim

Bcl-2

Bax

MDM2

Bad

14-3-3

p53

CHK1 CHK2

ATMATR

PI3K

GßL Rictor

mTOR

SIN1

PI3K

Lyn

PDK1

PTEN PP2A PHLPP CTMP

Ag

BCAP

Syk

PI3K Gßy G

GTP

IL2

IL2R

Jak1GPCR

Akt Signaling Pathway

www.rockland-inc.com

G-6-Pase

GlycogenSynthase

F-1,6-Pase PEPCK

Glucose

Glucose

Glucose-6-P

Glycogen

Glucose

GK

PFK

Pyruvate

PK

SREBP

Mitochondria

Insulin Receptor

Stimulatedby Insulin

Inhibitedby Insulin

Gene expression

HNF/FoxA

PGC1

Citrate

Acetyl-CoA

Acyl-CoA

Malonyl-CoA

Citratelyase

ACC

FASGlucose Regulation

RelBp50 p50

CanonicalTNF , IL-1

LPSCD40L

p105TNF , IL-1

LPS

Alternative (p100)LT , LTß

CD40LBAFF

RANKL

NEMO

IKK-1 IKK-2

NEMO

IKK-1 IKK-2 IKK-1 IKK-1

P105

p50p50

p50p50

P100

RelBp52

p50

RelA

RelBp52

RelA

p50

RelAp50

Target Genes

(MEKK3, TAK1) MAP3-K NIK

Nucleus

I B-

NF B

p53 R2Transducers

MDM2p53

CBPP300

ASPP1

TRAFPCAF

p53

Active p53

maspin GD-AIF

tsp1 Bal-I

p21

GADD45

14-3-3p48

GADD45 XPC

Angiogenesis Growth Arrest DNA Repair

DR5 Pig3

AIP1 Noxa

Bax Bax

Puma Fas

Apoptosis

Outcome

Effectors

p53: The Master Switch

P

P

Ub

P

P

Pp27

(KIP1)

Cyclin-A

S-Phase Genes[Cyclin-A, E, E2F, CDC2]

Raf1

Cell CycleProgression

Cyclin-A

Wee1

CDK2

CDC-25A

Cyclin-H

CDK7

E2F

Rb

CDK2

Ub

P

P

P

p21

p27(KIP1)

P

Ub

Rb

E2F

SCF

p27 (KIP1)Degredation

DP1E2F

Cell Cycle S-Phase

Kinase

Phosphatase

Life

TranscriptionFactor

Enzyme

Death

Stimulatory

Inhibitory

Tentative Block

Translocation

Key