$654.00

I2PP2A-GST (5 μg)
[GLO145-005]

Source: Recombinant human kidney produced GST-tagged in E. coli

Purity: > 90% by SDS-PAGE, apparent Mr ~ 67-kDa

Supplied: 5 μg in 50 μl 50 mM Tris-HCl pH 7.0 buffer containing 14 mM β-mercaptoethanol, 1 mM benzamidine, 0.1 mM phenylmethanesulfonyl fluoride, 1 mM EDTA, 0.1% Brij-35 and 10% glycerol. Maintain preparations in aliquots at -70° C. Avoid repeated thawing.

Synonyms: GST-I2PP2A; Protein Phosphatase 2A Inhibitor Protein 2; SET; PHAP-II; Taf-1β

BackgroundThe 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 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). LikeI1PP2A, 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 was also shown to be highly expressed in Wilms tumor but not in renal cell carcinoma, adult polycystic kidney disease or in transitional cell carcinoma.  I2PP2A 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 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. Evidence exists that 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. 

GLoboZymes I2PP2A GST-tagged preparations maintain all known activities of the native I2PP2A protein (GLO141-001) tested to date. The GST-tagged preparations can also be used for binding and pull-down studies.

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 ProductsI2PP2A  ♦  I2PP2A GST (1 μg)  ♦  Anti-I2PP2A (100 μg)  ♦  Anti-I2PP2A (200 μg)  ♦  I2PP2A Detection Kit  ♦  I2PP2A(β)  ♦ I1PP2A ♦  I1PP2A GST (1 μg)  ♦  I1PP2A GST (5 μg)  ♦  PP2A1 ♦  PP2A2 ♦  PP2AC ♦  PP1C ♦ MBP (10 mg)  ♦ MBP (25 mg)

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