All tags p53 Regulation of p53

Regulation of p53

The tumor suppressor p53 is highly regulated at the transcriptional, translational and protein level. Below we discuss the different ways p53 is regulated and suggest our top products for your p53 modification research. 

The role of MDM2

The E3 ubiquitin-protein ligase, MDM2, regulates p53 by facilitating its destruction. MDM2 binds to p53 and mediates the covalent attachment of ubiquitin to p53 – this is then degraded by the proteasome1,2,3.

Get your project underway with antibodies, inhibitors and recombinant proteins to study MDM2 and p53.


MDM2p53
Antibody Anti-MDM2 antibody [2A10] Anti-p53 antibody [DO-1]
Anti-MDM2 (phospho S166) antibody 
Small molecule(-)-Nutlin-3Pifithrin 
Rita 
Recombinant protein Recombinant Human MDM2 protein Recombinant Human p53 protein 


Post-translational modifications of p53

​​When the cell is confronted with stress, p53 ubiquitylation is suppressed and p53 accumulates in the nucleus, where it is activated and stabilized by undergoing interdependent modifications including phosphorylation and acetylation.

Upon activation, p53 then mediates transcription of relevant target genes, with the help of its transcriptional co-regulators, to induce the desired response5,6,7.


p53 phosphorylation
Phosphorylation of p53 is induced by DNA damage. p53 contains multiple serine and threonine residues that serve as phosphorylation sites for protein kinases. These kinases include ATM/ATR, Chk1/Chk2, CK1, CK2, PKC, CDK1/2, DNA-PK, HIPK2, ERK2, p38 and JNK.

Figure 1. p53 phosphorylation sites. Protein kinases and their respective phosphorylation sites on the p53 protein. Click to expand. 

Antibodies for p53 modification research:​​

Amino acidRecommended abApplication
S9Anti-p53 (phospho S9) antibody ELISA, IHC-P, WB
S15Anti-p53 (phospho S15) antibody ICC/IF, IHC-Fr, IHC-P, IP, WB
S20Anti-p53 (phospho S20) antibody IP, WB
S33Anti-p53 (phospho S33) antibodyICC/IF, WB
S37Anti-p53 (phospho S37) antibody Dot, WB
S46Anti-p53 (phospho S46) antibodyICC/IF, IHC-P, IP, WB

p53 acetylation
p53 is specifically acetylated by p300/CBP and P300/CBP-associated factor (PCAF) in response to gamma-irradiation and UV light, and TIP60 and hMOF in response to DNA damage. Acetylation of p53 augments p53 DNA binding, aids in recruiting co-activators, and stabilizes p53 by inhibiting its ubiquitination by MDM24,5,6,7.

Figure 2. p53 acetylation (A), methylation (M), and ubiquitylation (Ub) sites. Protein kinases and their respective modification sites on the p53 protein. Click to expand. ​

Antibodies for p53 modification research:

Amino acidRecommended abApplication
K370Anti-p53 (acetyl K370) antibody Flow Cyt, ICC/IF, IP, WB
K373Anti-p53 (acetyl K373) antibody Flow Cyt, ICC/IF, IHC-P, WB
K381Anti-p53 (acetyl K381) antibodyELISA, ICC, IHC-P, WB
K382Anti-p53 (acetyl K382) antibody ICC, IHC-P, WB

References

  • 1. Nag S, Qin J, Srivenugopal KS, Wang M, Zhang R. 2013. The MDM2-p53 pathway revisited. J Biomed Res. 27(4):254-71. doi: 10.7555/JBR.27.20130030.
  • 2. Levine AJ, Oren M. 2009. The first 30 years of p53: growing ever more complex. Nat Rev Cancer. 9(10):749-58. doi: 10.1038/nrc2723.
  • 3. Hasty P, Christy BA. 2013. p53 as an intervention target for cancer and aging. Pathobiol Aging Age Relat Dis. 3:22702. doi: 10.3402/pba.v3i0.22702.
  • 4. Vousden KH, Prives C. 2009. Blinded by the light: the growing complexity of p53. Cell. 137(3):413-31. doi: 10.1016/j.cell.2009.04.037.
  • 5. Xu Y. 2003. Regulation of p53 responses by post-translational modifications. Cell Death Differ. 10(4):400-3.
  • 6. Meek DW, Anderson CW. 2009. Posttranslational modification of p53: cooperative integrators of function. Cold Spring Harb Perspect Biol. 1(6):a000950. doi:10.1101/cshperspect.a000950.
  • 7. Olsson A, Manzl C, Strasser A, Villunger A. 2007. How important are post-translational modifications in p53 for selectivity in target-gene transcription and tumour suppression? Cell Death Differ. 14(9):1561-75.