AP09871PU-N OriGene Technologies Inc. OriGene EU

Acris Antibodies GmbH 9620 Medical Center Drive, Ste 200 Schillerstr. 5 Rockville, MD 20850 32052 Herford UNITED STATES GERMANY Phone: +1-888-267-4436 Phone: +49-5221-34606-0 Fax: +1-301-340-8606 Fax: +49-5221-34606-11 [email protected] [email protected]

Polyclonal Antibody to Sestrin-3 (SESN3) (N-term) - Aff - Purified Alternate names: SEST3 Catalog No.: AP09871PU-N Quantity: 0.1 mg Concentration: 0.70 mg/ml Background: Sestrin 3(SESN3), located at human 11q21, belongs to the sestrin family of . These proteins are cystein sulfinyl reductases and they modulate peroxide signaling and antioxidant defense (1). This family of proteins is only present in multicellular organisms ranging from nematodes to mammals. These proteins selectively reduce or repair hyperoxidized forms of typical 2-Cys peroxiredoxins within eukaryotes (2). Peroxiredoxins are the enzymes that metabolize peroxides. Expression of these proteins is regulated by p53, a tumor suppressor (3). Sestrin 3 was identified as a forkhead box O (FoxO) target with antioxidant activity (4). Recently it was reported that sestrin 3 may play an important role in AKT induced increase in ROS and it might be a promising target in selectively killing cancer cells containing high levels of AKT activity (5). AKT is a protein kinase that is hyperactivated in cancer. This hyperactivity leads to an increase in intracellular ROS mainly by inhibiting the expression of ROS scavengers downstream of FoxO, such as sestrin 3 (4). This phenomenon was supported by the fact that AKT deficient cells contained high levels of sestrin 3 leading to low levels of ROS. Furthermore, downregulation of sestrin 3 restored ROS levels in these cells (5). Hyperactivation of AKT has been shown to promote uncontrolled cell growth and also protect cells from apoptosis (6). Inhibition of mRNAs from sestrin 3 as well as from sestrin 1 has also been shown to substantially increase intracellular ROS levels. This increase in ROS is linked to Ras-induced mutagenesis which is one of the most common events in cancer (7). Sestrin 3 is approximately a 38.5kDa protein (480 amino acids) in human and 59kDa protein (492 amino acids) in rat and mouse. Uniprot ID: P58005 NCBI: NP_653266 GeneID: 143686 Host: Rabbit Immunogen: Synthetic peptide corresponding to Human Sestrin-3 selected from N-terminal region (aa 1-50) Remarks: The peptide was post-synthetically covalently modified to achieve desired antigenicity.

For research and in vitro use only. Not for diagnostic or therapeutic work. MT/20140115 Material Safety Datasheets are available at www.acris-antibodies.com or on request. Acris Antibodies is now part of the OriGene family. Learn more at www.origene.com 1 / 2 AP09871PU-N: Polyclonal Antibody to Sestrin-3 (SESN3) (N-term) - Aff - Purified Format: State: Liquid purified Ig fraction Purification: Antigen-Immobilized Affinity Chromatography Buffer System: Stabilization buffer Applications: Suitable for use in ELISA (< 1/10,000) and Western Blot (> 1/500). Other applications not tested. Optimal dilutions are dependent on conditions and should be determined by the user. Specificity: This antibody will label ~59kDa protein in Western blot positive control samples for SESN3 and several other tissues. Species: Human, Mouse and Rat. Other species not tested. Add. Information: Antigenic blocking peptide (AP09871CP-N) for Sestrin-3 is also available separately. Storage: Store the antibody undiluted (in aliquots) at -20°C. Avoid repeated freezing and thawing. Shelf life: one year from despatch. General Readings: 1. Meiller A, Alvarez S, Drané P, Lallemand C, Blanchard B, Tovey M, et al. p53-dependent stimulation of redox-related in the lymphoid organs of gamma-irradiated--mice identification of Haeme-oxygenase 1 as a direct p53 target gene. Nucleic Acids Res. 2007;35(20):6924-34. Epub 2007 Oct 11. PubMed PMID: 17933770. 2. Jönsson TJ, Lowther WT. The peroxiredoxin repair proteins. Subcell Biochem. 2007;44:115-41. PubMed PMID: 18084892. 3. Budanov AV, Sablina AA, Feinstein E, Koonin EV, Chumakov PM. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science. 2004 Apr 23;304(5670):596-600. PubMed PMID: 15105503. 4. Nogueira V, Park Y, Chen CC, Xu PZ, Chen ML, Tonic I, et al. Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis. Cancer Cell. 2008 Dec 9;14(6):458-70. doi: 10.1016/j.ccr.2008.11.003. PubMed PMID: 19061837. 5. Dolado I, Nebreda AR. AKT and oxidative stress team up to kill cancer cells. Cancer Cell. 2008 Dec 9;14(6):427-9. doi: 10.1016/j.ccr.2008.11.006. PubMed PMID: 19061832. 6. Kandel ES, Skeen J, Majewski N, Di Cristofano A, Pandolfi PP, Feliciano CS, et al. Activation of Akt/protein kinase B overcomes a G(2)/m cell cycle checkpoint induced by DNA damage. Mol Cell Biol. 2002 Nov;22(22):7831-41. PubMed PMID: 12391152. 7. Kopnin PB, Agapova LS, Kopnin BP, Chumakov PM. Repression of sestrin family genes contributes to oncogenic Ras-induced reactive oxygen species up-regulation and genetic instability. Cancer Res. 2007 May 15;67(10):4671-8. PubMed PMID: 17510393. Pictures: Western Blot of Sestrin-3 antibody (Cat#AP09871PU-N) at 1/500 dilution.

For research and in vitro use only. Not for diagnostic or therapeutic work. MT/20140115 Material Safety Datasheets are available at www.acris-antibodies.com or on request. Acris Antibodies is now part of the OriGene family. Learn more at www.origene.com 2 / 2

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