Regulation of Tumor Suppressor p53

Introduction

p53 is a tumor suppressor which is highly regulated at the translational, transcriptional, and protein level. This article discusses the different approaches used for p53 regulation, and suggests the top products offered by Abcam for p53 modification research.

The role of MDM2

MDM2 is an E3 ubiquitin-protein ligase used for p53 regulation by facilitating the destruction of the tumor suppressor. MDM2 attaches to p53 and mediates the covalent bonding of ubiquitin to p53, which is then degraded by the proteasome1,2,3.

Abcam offers recombinant proteins, inhibitors, and antibodies to study MDM2 and p53.

Antibody

Anti-MDM2 antibody [2A10]

Anti-p53 antibody [DO-1]

Anti-MDM2 (phospho S166) antibody

Small molecule

(-)-Nutlin-3

Pifithrin

Rita

Recombinant protein

Recombinant Human MDM2 protein

Recombinant Human p53 protein

Post-translational modifications of p53

Suppression of p53 ubiquitylation occurs when a cell is exposed to stress, which, in turn, causes accumulation of p53 in the nucleus. Then, p53 is activated and stabilized in the nucleus by undergoing interdependent modifications such as acetylation and phosphorylation.

Following activation, transcription of relevant target genes is mediated by p53 using its transcriptional co-regulators, in order to trigger the desired response5,6,7.

p53 phosphorylation

DNA damage induces p53 phosphorylation. The presence of multiple threonine and serine residues in p53 serves as phosphorylation sites for protein kinases, which include JNK, p38, ERK2, HIPK2, DNA-PK, CDK1/2, PKC, CK1, CK2, Chk1/Chk2, and ATM/ATR.

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

The following are the antibodies offered by Abcam for p53 modification research:

Amino acid

Recommended ab

Application

S9

Anti-p53 (phospho S9) antibody

ELISA, IHC-P, WB

S15

Anti-p53 (phospho S15) antibody

ICC/IF, IHC-Fr, IHC-P, IP, WB

S20

Anti-p53 (phospho S20) antibody

IP, WB

S33

Anti-p53 (phospho S33) antibody

ICC/IF, WB

S37

Anti-p53 (phospho S37) antibody

Dot, WB

S46

Anti-p53 (phospho S46) antibody

ICC/IF, IHC-P, IP, WB

p53 acetylation

p53 acetylation by p300/CBP and P300/CBP-associated factor (PCAF) is specifically performed in response to gamma-irradiation and UV light, and by TIP60 and hMOF in response to DNA damage. p53 acetylation aids in recruiting co-activators, promotes p53 DNA binding, and stabilizes p53 by suppressing 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.

Antibodies available from Abcam for p53 modification research are listed in the following table:

Amino acid

Recommended ab

Application

K370

Anti-p53 (acetyl K370) antibody

Flow Cyt, ICC/IF, IP, WB

K373

Anti-p53 (acetyl K373) antibody

Flow Cyt, ICC/IF, IHC-P, WB

K381

Anti-p53 (acetyl K381) antibody

ELISA, ICC, IHC-P, WB

K382

Anti-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.

About Abcam

Abcam is a global life sciences company providing highly validated antibodies and other binders and assays to the research and clinical communities to help advance the understanding of biology and causes of disease.

Abcam’s mission is to serve life scientists to help them achieve their mission faster by listening to their needs, continuously innovating and improving and by giving them the tools, data and experience they want. Abcam’s ambition is to become the most influential life science company for researchers worldwide.

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Last updated: Feb 5, 2018 at 5:23 AM

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