$549.00

Anti-I2PP2A (200 μg)
[GLO150-100]

Description: Anti-I2PPA/SET is an affinity-purified polyclonal antibody. It was produced in rabbits against a synthetic peptide corresponding to residues 3 to 18 of human kidney I2PPA/SET. The antibody is specific for I2PPA/SET and does not cross-react with I2PPA(b) (also termed TAF-1a). It is useful for Western blotting, for example, with 10 μg of HEK293 cell extracts at 1:1000 dilution of the antibody. The antibody is effective also for in situ immumofluoresence labeling. 

Synonyms: Antibody to Protein Phosphatase 2A Inhibitor Protein 2.  

Background: The PP2A inhibitor proteins, I1PP2A and I2PP2A, were discovered in the laboratory of GloboZymes founder Dr. Zahi Damuni while he was a faculty member in the Department of Cellular and Molecular Physiology at Penn State College of Medicine. There has been progress since that time in numerous laboratories around the world demonstrating further the significance of these proteins in various diseases including cancer and Alzheimers, for example. I2PP2A (GLO141-001) is also known as putative histocompatibility leukocyte antigen class II protein (PHAP-II), template activating factor 1 (Taf-1β), and inhibitor of histone acetyltransferase (INHAT). Like I1PP2A, it is a potent noncompetitive inhibitor of Protein Phosphatase 2A (PP2A), a major mammalian protein serine/threonine phosphatase that regulates diverse cellular processes. Purified preparations of I2PP2A inhibit all forms of the phosphatase (GLO130-132) tested to date in a substrate selective manner. For example, the preparations inhibit PP2A potently (ki ~ 0.1 - 0.5 nM) with myelin basic protein (MBP,GLO126-010MGLO126-025) and histone H1 but not with casein as substrate. In a patient with acute undifferentiated leukemia, I2PP2A was found to occur as a fusion protein with the nucleoporin CAN (NUP214) apparently produced by a somatic translocation event. I2PP2A is also highly expressed in Wilms tumor but not in renal cell carcinoma, adult polycystic kidney disease or in transitional cell carcinoma.  The inhibitor protein also associates with HRX leukemia-associated fusion proteins. Elevated expression of I1PP2A and I2PP2A in the brain of Alzheimers patients has been noted and is believed to contribute, at least in part, to the hyperphosphorylation of Tau protein via the inhibition of PP2A. Transient expression of I2PP2A in HEK-293 cells leads to an increase in the DNA binding activity of the proto-oncogene c-Jun consistent with the suppression of PP2A activity in intact cells. The apoptotic sphingolipid second messenger cermaide has been shown to bind I2PP2A and prevent it from inhibiting PP2A. This is believed to contribute to the mechanism by which ceramide promotes apoptosis. I2PP2A also prevents inhibition of E-CDK-2 by p21Cip1, associates with B cyclin, regulates histone binding to DNA, transcriptional activity and chromatin condensation. I2PP2A undergoes phosphorylation at Ser9 and Ser24 in intact cells. The functional significance of these phosphorylations is uncertain although recent studies indicate that Ser9 phosphorylation may causes cytoplasmic detention of I2PP2A in Alzheimer disease. 

References

  1. Li M, Makkinje A, Damuni Z.  (1996) "The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A"  J Biol Chem 271, 11059-11062
  2. von Lindern, M. et al (1992)  "Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3' half to different genes: characterization of the set gene"  Mol Cell Biol 12, 3346-3355
  3. Adler, H.T. et al (1997) "HRX leukemic fusion proteins form a heterocomplex with the leukemia-associated protein SET and protein phosphatase 2A" J Biol Chem.  272, 28407-28414
  4. Gong-Ping, L. et al  (2012)  "I2PP2A regulates p53 and Akt correlatively and leads the neurons to abort apoptosis" Neurobiology of Aging 33, 254-264
  5. Al-Murrani, S. W., Woodgett, J. R., and Damuni, Z. (1999) "Expression of I2PP2A, an inhibitor of protein phosphatase 2A, induces c-Jun and AP-1 activity" Biochem J. 341, 293–298
  6. Chambon, J.-P. et al (2013) "The PP2A Inhibitor I2PP2A Is Essential for Sister Chromatid Segregation in Oocyte Meiosis II"  Current Biol 23, 485-490
  7. Saddoughi, S. A. et al (2102)  "Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosis" EMBO Mol Med 5, 105-121
  8. Switzer, C. H. et al (2011) "Targeting SET/I2PP2A oncoprotein functions as a multi-pathway strategy for cancer therapy"  Oncogene 30, 2504–2513
  9. Li, M., Damuni, Z. (1998) "I1PP2A and I2PP2A: Two Potent Protein Phosphatase 2A-Specific Inhibitor Proteins" Methods Mol Biol  93, 59-66
  10. Katayose, Y. et al (2000) "Protein Phosphatase 2A Inhibitors, I1PP2A and I2PP2A, Associate with and Modify the Substrate Specificity of Protein Phosphatase 1" J Biol Chem 275, 9209-9214
  11. Saddoughi, S. A. et al (2010) "Direct interaction between ceramide and SET/I2PP2A restores nuclear PP2A activity leading to the degradation of cMyc and suppression of lung tumor growth" Clin Cancer Res 16, A26
  12. Yu, G. et al (2013) "Ser9 phosphorylation causes cytoplasmic detention of I2PP2A/SET in Alzheimer disease" Neurobiol Aging 34, 1748-1758
  13. Harmala-Brasken, A. S. et al (2003) “Type-2A protein phosphatase activity is required to maintain death receptor responsiveness” Oncogene 22, 7677-7686
  14. Tanimukai, H. et al (2005) "Up-regulation of inhibitors of protein phosphatase 2A in Alzheimer's disease" Am J Pathol. 166, 1761-1771
  15. Mukhopadhyay, A. et al (2009) "Direct interaction between the inhibitor 2 and ceramide via sphingolipid-protein binding is involved in the regulation of protein phosphatase 2A activity and signaling" FASEB J 23, 751-763

Related ProductsAnti-I2PP2A (200 μg)  ♦  I2PP2A Detection Kit  ♦  I2PP2A ♦  I2PP2A-GST (1 μg)  ♦  I2PP2A-GST (5 μg)  ♦  I2PP2A(β) ♦  I1PP2A ♦  I1PP2A-GST (1 μg)  ♦  I1PP2A-GST (5 μg)   ♦  PP2A1 ♦  PP2A2 ♦ PP2AC ♦  PP1C

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