Phospho-p53 (Ser46) AntibodyProduct information
Product Pathways - DNA Damage
Phospho-p53 (Ser46) Antibody #2521
|2521S||100 µl (10 western blots)||---||In Stock||---|
|2521T||20 µl (2 western blots)||---||In Stock||---|
|2521||carrier free and custom formulation / quantity||email request|
Species cross-reactivity is determined by western blot.
Applications Key: W=Western Blotting, IP=Immunoprecipitation, IF-IC=Immunofluorescence (Immunocytochemistry), F=Flow Cytometry
Specificity / Sensitivity
Phospho-p53 (Ser46) Antibody detects endogenous levels of p53 only when phosphorylated at serine 46. The antibody does not cross-react with p53 phosphorylated at other sites.
Source / Purification
Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser46 of human p53. Antibodies are purified by protein A and peptide affinity chromatography.
Western blot analysis of extracts from MCF-7 cells treated with etoposide for the indicated times, using Phospho-p53 (Ser46) Antibody.
Immunoprecipitation of extracts from MCF-7 cells treated with etoposide under nondenaturing conditions, using Phospho-p53 (Ser46) Antibody, followed by Western blot analysis using a monoclonal p53 antibody.
Confocal immunofluorescent analysis of MCF-7 cells, untreated (left) or etoposide-treated (right), using Phospho-p53 (Ser46) Antibody (green). Actin filaments have been labeled with DY-554 phalloidin (red).
The p53 tumor suppressor protein plays a major role in cellular response to DNA damage and other genomic aberrations. Activation of p53 can lead to either cell cycle arrest and DNA repair or apoptosis (1). p53 is phosphorylated at multiple sites in vivo and by several different protein kinases in vitro (2,3). DNA damage induces phosphorylation of p53 at Ser15 and Ser20 and leads to a reduced interaction between p53 and its negative regulator, the oncoprotein MDM2 (4). MDM2 inhibits p53 accumulation by targeting it for ubiquitination and proteasomal degradation (5,6). p53 can be phosphorylated by ATM, ATR, and DNA-PK at Ser15 and Ser37. Phosphorylation impairs the ability of MDM2 to bind p53, promoting both the accumulation and activation of p53 in response to DNA damage (4,7). Chk2 and Chk1 can phosphorylate p53 at Ser20, enhancing its tetramerization, stability, and activity (8,9). p53 is phosphorylated at Ser392 in vivo (10,11) and by CAK in vitro (11). Phosphorylation of p53 at Ser392 is increased in human tumors (12) and has been reported to influence the growth suppressor function, DNA binding, and transcriptional activation of p53 (10,13,14). p53 is phosphorylated at Ser6 and Ser9 by CK1δ and CK1ε both in vitro and in vivo (13,15). Phosphorylation of p53 at Ser46 regulates the ability of p53 to induce apoptosis (16). Acetylation of p53 is mediated by p300 and CBP acetyltransferases. Inhibition of deacetylation suppressing MDM2 from recruiting HDAC1 complex by p19 (ARF) stabilizes p53. Acetylation appears to play a positive role in the accumulation of p53 protein in stress response (17). Following DNA damage, human p53 becomes acetylated at Lys382 (Lys379 in mouse) in vivo to enhance p53-DNA binding (18). Deacetylation of p53 occurs through interaction with the SIRT1 protein, a deacetylase that may be involved in cellular aging and the DNA damage response (19).
Homeodomain-interacting protein kinase 2 (HIPK2) Phosphorylates Ser46 off p53 in vitro and in vivo (17,18), and p38 can phosphorylate this site in vitro (19).
- Levine, A.J. (1997) Cell 88, 323-31.
- Meek, D.W. (1994) Semin Cancer Biol 5, 203-10.
- Milczarek, G.J. et al. (1997) Life Sci 60, 1-11.
- Shieh, S.Y. et al. (1997) Cell 91, 325-34.
- Chehab, N.H. et al. (1999) Proc Natl Acad Sci U S A 96, 13777-82.
- Honda, R. et al. (1997) FEBS Lett 420, 25-7.
- Tibbetts, R.S. et al. (1999) Genes Dev 13, 152-7.
- Shieh, S.Y. et al. (1999) EMBO J 18, 1815-23.
- Hirao, A. et al. (2000) Science 287, 1824-7.
- Hao, M. et al. (1996) J Biol Chem 271, 29380-5.
- Lu, H. et al. (1997) Mol Cell Biol 17, 5923-34.
- Ullrich, S.J. et al. (1993) Proc Natl Acad Sci U S A 90, 5954-8.
- Kohn, K.W. (1999) Mol Biol Cell 10, 2703-34.
- Lohrum, M. and Scheidtmann, K.H. (1996) Oncogene 13, 2527-39.
- Knippschild, U. et al. (1997) Oncogene 15, 1727-36.
- Oda, K. et al. (2000) Cell 102, 849-62.
- Ito, A. et al. (2001) EMBO J 20, 1331-40.
- Sakaguchi, K. et al. (1998) Genes Dev 12, 2831-41.
- Solomon, J.M. et al. (2006) Mol Cell Biol 26, 28-38.
- D'Orazi, G. et al. (2002) Nat. Cell Biol. 4, 11-19.
- Hofmann, T. G. et al. (2002) Nat. Cell Biol. 4, 1-10.
- Bulavin, D. V. et al. (1999) EMBO J. 18, 6845-6854.
- Wang, C. and Chen, J. (2003) J Biol Chem 278, 2066-71. Applications: Western Blotting.
Have you published research involving the use of our products? If so we'd love to hear about it. Please let us know!
- 7074 Anti-rabbit IgG, HRP-linked Antibody
- 9915 Apoptosis Antibody Sampler Kit
- 7727 Biotinylated Protein Ladder Detection Pack
- 9286 Phospho-p53 (Ser15) (16G8) Mouse mAb
- 9284 Phospho-p53 (Ser15) Antibody
- 9287 Phospho-p53 (Ser20) Antibody
- 9289 Phospho-p53 (Ser37) Antibody
- 9281 Phospho-p53 (Ser392) Antibody
- 9285 Phospho-p53 (Ser6) Antibody
- 9288 Phospho-p53 (Ser9) Antibody
- 9919 Phospho-p53 Antibody Sampler Kit
- 6883 SignalFire™ ECL Reagent
- 12757 SignalFire™ Elite ECL Reagent
- 12630 SignalFire™ Plus ECL Reagent
- 2524 p53 (1C12) Mouse mAb
- 2527 p53 (7F5) Rabbit mAb
- 9282 p53 Antibody
This product is intended for research purposes only. The product is not intended to be used for therapeutic or diagnostic purposes in humans or animals.
Cell Signaling Technology is a trademark of Cell Signaling Technology, Inc.