p53 Pathway

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AMPK
AMPK
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p53
p53
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PTEN
PTEN
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TSC1/2
TSC1/2
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Akt
Akt
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Rheb
Rheb
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mTORC1
mTORC1

Autophagy
Induction

Autophagy
Induction

Translation
Inhibition

Translation
Inhibition

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p53
p53
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Bcl-2/Bcl-xL
Bcl-2/Bcl-xL
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Bad
Bad
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BAK
BAK
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Bax
Bax
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Cytochrome c
Cytochrome c

Apoptosis

Apoptosis

Low Nutrients
Low Nutrients
Catastrophic Stress
Catastrophic Stress
Basal/No Stress
Basal/No Stress
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USP2
USP2
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UbcH5
UbcH5
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MDM2
MDM2
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USP4
USP4
p53
p53
26S Proteasome
26S Proteasome

p53
Degradation

p53
Degradation

Oncogenic Stress
Oncogenic Stress
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MDM2
MDM2
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p53
p53
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DNA Damage
DNA Damage
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ATM
ATM
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ATR
ATR
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ATRIP
ATRIP
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Chk2
Chk2
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Chk1
Chk1
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MDM2
MDM2
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p53
p53
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p21
p21
14-3-3 sigma
14-3-3 sigma
GADD45 alpha
GADD45 alpha
Cyclin D
Cyclin D
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CDK4/6
CDK4/6
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Cyclin E
Cyclin E
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CDK2
CDK2
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Cyclin B
Cyclin B
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Cdc2/CDK1
Cdc2/CDK1
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Cell Cycle
Arrest/DNA
Repair

Cell Cycle
Arrest/DNA
Repair

Nucleolar Stress
Nucleolar Stress
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Nucleolus
Nucleolus
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MDM2
MDM2
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p53
p53
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p53
p53
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Apoptosis
Apoptosis
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p53
p53
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Autophagy
Autophagy
Cell Cycle Arrest
Cell Cycle Arrest
DNA Repair
DNA Repair
Metabolism
Metabolism
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p53
p53
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Senescence
Senescence
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p53
p53
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Tumor Microenvironment
Tumor Microenvironment
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Sestrin1/2
Sestrin1/2
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ARF-BP1
ARF-BP1
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PIRH2
PIRH2
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ARF
ARF
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PCNA
PCNA
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ARF
ARF
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Ribosomal
Proteins
Ribosomal
Proteins
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Ras
Ras
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MDMX
MDMX

Overview of p53 Pathways

p53 is a transcription factor that is well known for its key role as a tumor suppressor protein. Mutations in the p53 gene are one of the most frequent genomic events accompanying oncogenic transformation. Because of its critical cellular roles, p53 expression is tightly regulated post-translationally. Under basal conditions, p53 protein levels are negatively regulated by E3 ubiquitin ligases, including MDM2, which is the most widely studied. These E3 ligases promote the ubiquitination and subsequent proteasome-dependent degradation of p53. In response to stress stimuli, including DNA damage, nucleolar stress, metabolic stress, and oncogenic stress, p53 protein levels become stabilized. Once stable, p53 binds DNA as a homotetramer and activates the transcription of genes involved in many cellular processes that inhibit cancer progression, including apoptosis, cell cycle arrest, and senescence. p53 can also promote apoptosis independently of its transcriptional activity through interactions with Bcl-2 family proteins in the cytoplasm.

To learn more, please visit our p53 Pathway Research Area.

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