Interactome of Paraoxonase PON2 Reveals New Pathways for Tumor Growth Regulation

Overview

Journal Dokl Biochem Biophys

Specialties Biochemistry
Biophysics

Date 2023 Jan 18

PMID 36653584

Authors

V D Karlov

N B Pestov

M I Shakhparonov

T V Korneenko

Affiliations

Soon will be listed here.

Abstract

The interactome of paraoxonase-2 encoded by the PON2 gene was investigated. A cDNA library was screened using a yeast two-hybrid system to search for new proteins interacting with human PON2. Analysis of the identified candidates, along with previously published data on interactors obtained by other methods, indicates the presence of a significant number of indirect interactions between PON2 and EGFR and, consequently, possible regulation of tumor growth with mutant EGFR involving PON2.

Citing Articles

Effects of thymoquinone and the curcumin analog EF-24 on the activity of the enzyme paraoxonase-1 in human glioblastoma cells U87MG.

Simsek E, Sunguroglu A, Kilic A, Ozgultekin N, Ozensoy Guler O J Enzyme Inhib Med Chem. 2024; 39(1):2339901.

PMID: 38864175 PMC: 11172254. DOI: 10.1080/14756366.2024.2339901.

Paraoxonase 2 Deficiency Causes Mitochondrial Dysfunction in Retinal Pigment Epithelial Cells and Retinal Degeneration in Mice.

Sreekumar P, Su F, Spee C, Hong E, Komirisetty R, Araujo E Antioxidants (Basel). 2023; 12(10).

PMID: 37891899 PMC: 10604559. DOI: 10.3390/antiox12101820.

References

Sorenson R, Teiber J, La Du B . The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. Genomics. 1996; 33(3):498-507. DOI: 10.1006/geno.1996.0225. View

Nguyen T, Shin I, Lee T, Park J, Kim J, Park M . Loss of ITM2A, a novel tumor suppressor of ovarian cancer through G2/M cell cycle arrest, is a poor prognostic factor of epithelial ovarian cancer. Gynecol Oncol. 2015; 140(3):545-53. DOI: 10.1016/j.ygyno.2015.12.006. View

Shih D, Gu L, Xia Y, Navab M, Li W, Hama S . Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature. 1998; 394(6690):284-7. DOI: 10.1038/28406. View

Hagmann H, Kuczkowski A, Ruehl M, Lamkemeyer T, Brodesser S, Horke S . Breaking the chain at the membrane: paraoxonase 2 counteracts lipid peroxidation at the plasma membrane. FASEB J. 2014; 28(4):1769-79. DOI: 10.1096/fj.13-240309. View

Draganov D, Teiber J, Speelman A, Osawa Y, Sunahara R, La Du B . Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res. 2005; 46(6):1239-47. DOI: 10.1194/jlr.M400511-JLR200. View

Bourquard N, Ng C, Reddy S . Impaired hepatic insulin signalling in PON2-deficient mice: a novel role for the PON2/apoE axis on the macrophage inflammatory response. Biochem J. 2011; 436(1):91-100. PMC: 3743554. DOI: 10.1042/BJ20101891. View

Precourt L, Marcil V, NTimbane T, Taha R, Lavoie J, Delvin E . Antioxidative properties of paraoxonase 2 in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2012; 303(5):G623-34. PMC: 3468556. DOI: 10.1152/ajpgi.00039.2012. View

Li X, Li X, Hu F, Shen H, Cao J, Li Z . Association between paraoxonase 2 gene polymorphisms and noise-induced hearing loss in the Chinese population. J Occup Health. 2013; 55(2):56-65. DOI: 10.1539/joh.12-0242-oa. View

Mochizuki H, Scherer S, Xi T, Nickle D, Majer M, Huizenga J . Human PON2 gene at 7q21.3: cloning, multiple mRNA forms, and missense polymorphisms in the coding sequence. Gene. 1998; 213(1-2):149-57. DOI: 10.1016/s0378-1119(98)00193-0. View

10.

Rothem L, Hartman C, Dahan A, Lachter J, Eliakim R, Shamir R . Paraoxonases are associated with intestinal inflammatory diseases and intracellularly localized to the endoplasmic reticulum. Free Radic Biol Med. 2007; 43(5):730-9. DOI: 10.1016/j.freeradbiomed.2007.05.003. View

11.

Neill T, Schaefer L, Iozzo R . Decorin as a multivalent therapeutic agent against cancer. Adv Drug Deliv Rev. 2015; 97:174-85. PMC: 4753134. DOI: 10.1016/j.addr.2015.10.016. View

12.

Harel M, Aharoni A, Gaidukov L, Brumshtein B, Khersonsky O, Meged R . Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol. 2004; 11(5):412-9. DOI: 10.1038/nsmb767. View

13.

Shakhparonov M, Antipova N, Shender V, Shnaider P, Arapidi G, Pestov N . Expression and Intracellular Localization of Paraoxonase 2 in Different Types of Malignancies. Acta Naturae. 2018; 10(3):92-99. PMC: 6209399. View

14.

Shi S, Buck T, Nickerson A, Brodsky J, Kleyman T . Paraoxonase 2 is an ER chaperone that regulates the epithelial Na channel. Am J Physiol Cell Physiol. 2021; 322(1):C111-C121. PMC: 8759969. DOI: 10.1152/ajpcell.00335.2021. View

15.

Devarajan A, Bourquard N, Grijalva V, Gao F, Ganapathy E, Verma J . Role of PON2 in innate immune response in an acute infection model. Mol Genet Metab. 2013; 110(3):362-70. PMC: 3800229. DOI: 10.1016/j.ymgme.2013.07.003. View

16.

Yasmin I, Sundaram S, Banerjee A, Varier L, Dharmarajan A, Warrier S . Netrin-like domain of sFRP4, a Wnt antagonist inhibits stemness, metastatic and invasive properties by specifically blocking MMP-2 in cancer stem cells from human glioma cell line U87MG. Exp Cell Res. 2021; 409(2):112912. DOI: 10.1016/j.yexcr.2021.112912. View

17.

Horke S, Witte I, Wilgenbus P, Altenhofer S, Kruger M, Li H . Protective effect of paraoxonase-2 against endoplasmic reticulum stress-induced apoptosis is lost upon disturbance of calcium homoeostasis. Biochem J. 2008; 416(3):395-405. DOI: 10.1042/BJ20080775. View

18.

Watson A, Berliner J, Hama S, La Du B, Faull K, Fogelman A . Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest. 1995; 96(6):2882-91. PMC: 185999. DOI: 10.1172/JCI118359. View

19.

Jager S, Cimermancic P, Gulbahce N, Johnson J, McGovern K, Clarke S . Global landscape of HIV-human protein complexes. Nature. 2011; 481(7381):365-70. PMC: 3310911. DOI: 10.1038/nature10719. View

20.

Schweikert E, Amort J, Wilgenbus P, Forstermann U, Teiber J, Horke S . Paraoxonases-2 and -3 Are Important Defense Enzymes against Pseudomonas aeruginosa Virulence Factors due to Their Anti-Oxidative and Anti-Inflammatory Properties. J Lipids. 2012; 2012:352857. PMC: 3335252. DOI: 10.1155/2012/352857. View