Chemical genetic identification of the IGF-linked pathway that is mediated by STAT6 and MFP2

Chemistry & Biology
Yongmun ChoiMotonari Uesugi

Abstract

Insulin-like growth factor 2 (IGF2) is a potent mitogen whose deregulation plays a role in developing liver, breast, and prostate cancers. Here, we take a small-molecule approach to investigate molecular pathways that modulate IGF2 signaling, by using chromeceptin, a synthetic molecule that selectively impairs the viability and growth of IGF2-overexpressing hepatocellular carcinoma cells. Affinity purification revealed that chromeceptin binds to multifunctional protein 2 (MFP-2), a seemingly multifunctional enzyme implicated in peroxisomal beta-oxidation. The small molecule-protein interaction stimulates the expression of IGF binding protein 1 (IGFBP-1) and suppressor of cytokine signaling-3 (SOCS-3), two cellular attenuators of the IGF signals, through activation of signal transducers and activators of transcription 6 (STAT6). The results underline the importance of STATs in IGF/insulin regulation, and they implicate a new pathway for STAT6 activation that is amenable to small-molecule intervention.

References

Sep 16, 1994·Science·J HouS L McKnight
Apr 18, 1996·Nature·K TakedaS Akira
May 14, 1996·Proceedings of the National Academy of Sciences of the United States of America·P J BelshawS L Schreiber
Aug 4, 1999·Trends in Biochemical Sciences·C M Crews, U Splittgerber
Nov 23, 2000·Proceedings of the National Academy of Sciences of the United States of America·R T PetersonS L Schreiber
May 29, 2001·Molecular Pathology : MP·J G ScharfG Ramadori
Jun 8, 2001·Annual Review of Biochemistry·M MannA Pandey
Nov 1, 2001·Annual Review of Cell and Developmental Biology·M A Shogren-KnaakK M Shokat
Dec 12, 2001·Genome Biology·L RamdasW Zhang
Dec 19, 2001·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·K A BaggerlyW Zhang
Feb 2, 2002·Science·Ali H Brivanlou, James E Darnell
Mar 21, 2002·Nature Reviews. Cancer·P MarksW K Kelly
May 23, 2002·Bioinformatics·Ilya Shmulevich, Wei Zhang
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Matthew R RitterMartin Friedlander
May 30, 2002·Nucleic Acids Research·Angela RelógioJuan Valcárcel
Sep 14, 2002·The Journal of Biological Chemistry·Liangyou RuiMorris F White
Sep 20, 2002·Endocrinology·Josef V Silha, Liam J Murphy
Dec 24, 2002·The Journal of Biological Chemistry·Yongmun ChoiMotonari Uesugi
Dec 25, 2002·Chemistry & Biology·Jeffrey R Peterson, Timothy J Mitchison
May 14, 2003·Trends in Cell Biology·Thomas U Mayer
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniel HebenstreitJutta Horejs-Hoeck
Dec 6, 2003·Science·Morris F White
Mar 27, 2004·Blood·Chrystelle GuiterFlavia Castellano
Jun 8, 2004·The Journal of Biological Chemistry·Hang ShiJeffrey S Flier
Jun 17, 2004·The Journal of Biological Chemistry·Julia TravagliJosiane Pierre
Jul 1, 2004·Arthritis Research & Therapy·Lionel B Ivashkiv, Xiaoyu Hu
Jul 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kohjiro UekiC Ronald Kahn
Nov 16, 2004·Science·Christopher P AustinFrancis S Collins
Feb 25, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephen CanfieldPaul Rothman

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Citations

Aug 14, 2012·Nature Chemical Biology·Bert De RybelTom Beeckman
Oct 17, 2012·The Biochemical Journal·Dongju JungMotonari Uesugi
Jul 9, 2010·Chemistry & Biology·Shin-ichi SatoMotonari Uesugi
Oct 21, 2016·EBioMedicine·Naoya MatsunagaShigehiro Ohdo
Jun 13, 2012·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Motonari Uesugi
Nov 30, 2018·Journal of Agricultural and Food Chemistry·Yanli LiuXiaojun Yang
Jan 25, 2007·Journal of the American Chemical Society·Shin-Ichi SatoMotonari Uesugi
Nov 23, 2011·Bioorganic & Medicinal Chemistry·Etsu Tashiro, Masaya Imoto

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