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p53 Signaling

p53 is one of the most prominent tumor suppressors and is often called “the guardian of the genome”. Mutations of p53 or parts of its regulatory circuit are found in almost all cancers, which highlights its importance. It is conserving the stability of the genome by preventing mutations caused by cellular stress or DNA damage. p53 stabilizes the genome by regulating the expression of a wide variety of genes involved in Apoptosis, Inhibition of cell cycle progression, Differentiation, Growth arrest and accelerated DNA repair. p53 is a sequence-specific DNAbinding transcription factor which is maintained at low levels in mammalian cells which are not under cellular stress since p53 has a very short half-life. This is achieved through the continuous ubiquitination of p53 by its suppressor MDM2 and its subsequent degradation by the 26S Proteasome. Signals of cellular stress, like for example DNA damage, suppress the ubiquitylation of p53 and lead to its stabilization and activation. Once p53 is activated it binds to the regulatory elements of its downstream targets and regulates their transcription. This in turn starts several cellular programs which account for the different tumor-suppressing functions of p53. Written/Edited by Dr. Stefan Pellenz PhD

Angiogenesis

BAI1 (Brain-Specific Angiogenesis Inhibitor 1):

SERPINE1 - PAI1:

CD82 (CD82):

PRSS55 (Protease, Serine, 55):

SERPINB5 (serpin Peptidase Inhibitor, Clade B (Ovalbumin), Member 5):

Apoptosis

APAF1 (Apoptotic Peptidase Activating Factor 1):

PIDD (P53-Induced Death Domain Protein):

BBC3 - PUMA:

BAX (BCL2-Associated X Protein):

FAS (TNF Receptor Superfamily, Member 6):

MRPL41 (Mitochondrial Ribosomal Protein L41):

PMAIP1 - NOXA:

PDCD6IP - ALIX:

TNFRSF10B (Tumor Necrosis Factor Receptor Superfamily, Member 10b):

TP53I3 (Tumor Protein P53 Inducible Protein 3):

Core regulation

NRAS - GTPase NRas:

TP53 - p53:

MDM2 (Mdm2, p53 E3 Ubiquitin Protein Ligase Homolog (Mouse)):

DNA repair

RRM2B (Ribonucleotide Reductase M2 B (TP53 Inducible)):

XPC (Xeroderma Pigmentosum, Complementation Group C):

CRLF3 (Cytokine Receptor-Like Factor 3):

Effectors

PRDX1 - Peroxiredoxin 1:

PPP1R13B (Protein Phosphatase 1, Regulatory Subunit 13B):

EP300 - p300:

KAT2B (K(lysine) Acetyltransferase 2B):

PAG1 (phosphoprotein Associated with Glycosphingolipid Microdomains 1):

TANK (TRAF Family Member-Associated NFKB Activator):

Growth arrest

CDKN1A - p21:

GADD45A (Growth Arrest and DNA-Damage-Inducible, alpha):

SFN - 14-3-3 sigma/SFN:

Mediators

ATM (Ataxia Telangiectasia Mutated):

HMGB1 (High Mobility Group Box 1):

ARFGAP1 (ADP-Ribosylation Factor GTPase Activating Protein 1):

ATR (Ataxia Telangiectasia and Rad3 Related):

ATR Antibodies

CHEK1 (Checkpoint Kinase 1):

CHEK2 (Checkpoint Kinase 2):

NFKB1 (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells 1):

PML (Promyelocytic Leukemia):

SCYL1 (SCY1-Like 1):

TRIM29 (Tripartite Motif Containing 29):

Oncogene activation

HRAS (HRas proto-oncogene, GTPase):

MYC - c-MYC:

DMP1 (Dentin Matrix Acidic phosphoprotein 1):

E2F1 (E2F Transcription Factor 1):

NRAS - GTPase NRas:

TBX2 (T-Box 2):

TWIST1 (Twist Homolog 1 (Drosophila)):

Others

CCNG1 - Cyclin G1:

MAP4 (Microtubule-Associated Protein 4):

PPM1D (Protein Phosphatase, Mg2+/Mn2+ Dependent, 1D):

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Angiogenesis

BAI1 (Brain-Specific Angiogenesis Inhibitor 1):

SERPINE1 - PAI1:

CD82 (CD82):

PRSS55 (Protease, Serine, 55):

SERPINB5 (serpin Peptidase Inhibitor, Clade B (Ovalbumin), Member 5):

Apoptosis

APAF1 (Apoptotic Peptidase Activating Factor 1):

PIDD (P53-Induced Death Domain Protein):

BBC3 - PUMA:

BAX (BCL2-Associated X Protein):

FAS (TNF Receptor Superfamily, Member 6):

MRPL41 (Mitochondrial Ribosomal Protein L41):

PMAIP1 - NOXA:

PDCD6IP - ALIX:

TNFRSF10B (Tumor Necrosis Factor Receptor Superfamily, Member 10b):

TP53I3 (Tumor Protein P53 Inducible Protein 3):

Core regulation

NRAS - GTPase NRas:

TP53 - p53:

MDM2 (Mdm2, p53 E3 Ubiquitin Protein Ligase Homolog (Mouse)):

DNA repair

RRM2B (Ribonucleotide Reductase M2 B (TP53 Inducible)):

XPC (Xeroderma Pigmentosum, Complementation Group C):

CRLF3 (Cytokine Receptor-Like Factor 3):

Effectors

PRDX1 - Peroxiredoxin 1:

PPP1R13B (Protein Phosphatase 1, Regulatory Subunit 13B):

EP300 - p300:

KAT2B (K(lysine) Acetyltransferase 2B):

PAG1 (phosphoprotein Associated with Glycosphingolipid Microdomains 1):

TANK (TRAF Family Member-Associated NFKB Activator):

Growth arrest

CDKN1A - p21:

GADD45A (Growth Arrest and DNA-Damage-Inducible, alpha):

SFN - 14-3-3 sigma/SFN:

Mediators

ATM (Ataxia Telangiectasia Mutated):

HMGB1 (High Mobility Group Box 1):

ARFGAP1 (ADP-Ribosylation Factor GTPase Activating Protein 1):

ATR (Ataxia Telangiectasia and Rad3 Related):

CHEK1 (Checkpoint Kinase 1):

CHEK2 (Checkpoint Kinase 2):

NFKB1 (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells 1):

PML (Promyelocytic Leukemia):

SCYL1 (SCY1-Like 1):

TRIM29 (Tripartite Motif Containing 29):

Oncogene activation

HRAS (HRas proto-oncogene, GTPase):

MYC - c-MYC:

DMP1 (Dentin Matrix Acidic phosphoprotein 1):

E2F1 (E2F Transcription Factor 1):

NRAS - GTPase NRas:

TBX2 (T-Box 2):

TWIST1 (Twist Homolog 1 (Drosophila)):

Others

CCNG1 - Cyclin G1:

MAP4 (Microtubule-Associated Protein 4):

PPM1D (Protein Phosphatase, Mg2+/Mn2+ Dependent, 1D):

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