Nuclear MEK1 sequesters PPARĪ³ and bisects MEK1/ERK signaling: a non-canonical pathway of retinoic acid inhibition of adipocyte differentiation.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Adipocytes/*cytology ; MAP Kinase Kinase 1/*physiology ; PPAR gamma/*metabolism ; Tretinoin/*physiology; 3T3-L1 Cells ; Adipocytes/metabolism ; Adipogenesis ; Animals ; Cell Differentiation/genetics ; Karyopherins/metabolism ; MAP Kinase Kinase 1/metabolism ; MAP Kinase Signaling System ; Mice ; PPAR gamma/physiology ; Receptors, Cytoplasmic and Nuclear/metabolism ; Tretinoin/metabolism ; Exportin 1 Protein
    • Abstract:
      Uncontrolled adipogenesis and adipocyte proliferation have been connected to human comorbidities. Retinoic acid (RA) is known to inhibit adipocyte differentiation, however the underlying mechanisms have not been adequately understood. This study reports that RA acting as a ligand to RA receptors (RARs and RXRs) is not a sine qua non to the inhibition of adipogenesis. Our intriguing observation of a negative correlation between increased retinoylation and adipogenesis led us to explore retinoylated proteins in adipocytes. Exportin (CRM1) was found to be retinoylated, which in turn can affect the spatio-temporal regulation of the important signaling molecule mitogen-activated protein kinase kinase 1 (MEK1), likely by disrupting its export from the nucleus. Nuclear enrichment of MEK1 physically sequesters peroxisome proliferator-activated receptor gamma (PPARĪ³), the master regulator of adipogenesis, from its target genes and thus inhibits adipogenesis while also disrupting the MEK1-extracellular-signal regulated kinase (ERK) signaling cascade. This study is first to report the inhibition of adipocyte differentiation by retinoylation.
    • References:
      Biochem Biophys Res Commun. 1991 Oct 15;180(1):393-400. (PMID: 1718279)
      Cell Cycle. 2007 Jul 1;6(13):1539-48. (PMID: 17611413)
      Int J Obes Relat Metab Disord. 1999 Jan;23(1):1-6. (PMID: 10094571)
      FASEB J. 1996 Jul;10(9):940-54. (PMID: 8801176)
      Exp Cell Res. 1998 Aug 1;242(2):540-7. (PMID: 9683540)
      Eur J Biochem. 1993 Feb 15;212(1):13-26. (PMID: 8383035)
      Seikagaku. 2005 Jun;77(6):527-36. (PMID: 16022429)
      PLoS One. 2009;4(2):e4363. (PMID: 19204783)
      Mol Pharmacol. 2007 May;71(5):1251-7. (PMID: 17290005)
      Endocrinology. 2010 Nov;151(11):5247-54. (PMID: 20844002)
      Mol Cell Biol. 1996 Apr;16(4):1567-75. (PMID: 8657131)
      J Nutr Biochem. 2007 May;18(5):322-31. (PMID: 16963253)
      Can J Biochem Physiol. 1959 Aug;37(8):911-7. (PMID: 13671378)
      J Biochem. 2001 Sep;130(3):457-63. (PMID: 11530023)
      Arch Biochem Biophys. 1991 Feb 15;285(1):105-10. (PMID: 1990968)
      Metabolism. 2002 Nov;51(11):1407-9. (PMID: 12404189)
      Cell Metab. 2006 Oct;4(4):263-73. (PMID: 17011499)
      PLoS One. 2012;7(1):e30831. (PMID: 22292054)
      Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10807-11. (PMID: 1438281)
      J Bioenerg Biomembr. 2005 Feb;37(1):43-8. (PMID: 15906148)
      Biochim Biophys Acta. 1989 Sep 14;998(1):69-74. (PMID: 2790054)
      J Biol Chem. 1996 Aug 16;271(33):20024-8. (PMID: 8702720)
      Endocr Rev. 1999 Oct;20(5):649-88. (PMID: 10529898)
      Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3742-7. (PMID: 9108048)
      Skin Pharmacol. 1991;4(1):14-20. (PMID: 2064786)
      Immunochemistry. 1973 Apr;10(4):273-5. (PMID: 4737898)
      J Biol Chem. 1997 Apr 18;272(16):10811-6. (PMID: 9099735)
      J Biol Chem. 2002 Nov 29;277(48):46226-32. (PMID: 12270934)
      Br J Dermatol. 2010 May;162(5):974-9. (PMID: 19922530)
      Mol Cell Endocrinol. 2010 Jan 27;314(2):213-20. (PMID: 19406201)
      Mol Cell Biochem. 2005 Aug;276(1-2):55-60. (PMID: 16132685)
      EMBO J. 1995 Feb 15;14(4):674-84. (PMID: 7882971)
      Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9112-7. (PMID: 10430904)
      J Cell Biol. 1993 Sep;122(5):1079-88. (PMID: 8394845)
      J Lipid Res. 1996 Sep;37(9):1971-7. (PMID: 8895063)
      Science. 1996 Dec 20;274(5295):2100-3. (PMID: 8953045)
      Genes Dev. 2000 Jun 1;14(11):1293-307. (PMID: 10837022)
      Biochimie. 2005 Jan;87(1):51-6. (PMID: 15733737)
      Oncogene. 2001 Nov 15;20(52):7588-96. (PMID: 11753637)
      Yakugaku Zasshi. 2002 Aug;122(8):547-63. (PMID: 12187770)
      Biochem J. 1993 Aug 1;293 ( Pt 3):807-12. (PMID: 8394693)
      J Bioenerg Biomembr. 2010 Aug;42(4):321-8. (PMID: 20490639)
      Mol Endocrinol. 2006 Jul;20(7):1494-505. (PMID: 16484339)
      Annu Rev Pathol. 2011;6:345-64. (PMID: 21073338)
      Cell. 1994 Dec 30;79(7):1147-56. (PMID: 8001151)
      Comp Biochem Physiol Comp Physiol. 1993 Jul;105(3):485-92. (PMID: 8101780)
      Proc Natl Acad Sci U S A. 1980 May;77(5):2936-40. (PMID: 6930676)
      J Bioenerg Biomembr. 2008 Apr;40(2):111-5. (PMID: 18324454)
      Cell. 1997 Sep 19;90(6):1051-60. (PMID: 9323133)
      Mol Biol Cell. 2006 Feb;17(2):566-75. (PMID: 16280361)
      Nature. 1997 Nov 20;390(6657):308-11. (PMID: 9384386)
      Cell. 2008 Sep 19;134(6):921-31. (PMID: 18805086)
      J Lipid Res. 2002 Nov;43(11):1773-808. (PMID: 12401878)
      Nucleic Acids Res. 2012 Jan;40(Database issue):D388-93. (PMID: 22039152)
      J Biol Chem. 1989 Mar 25;264(9):5159-63. (PMID: 2925686)
      Biochim Biophys Acta. 2009 Jan;1791(1):3-7. (PMID: 18977311)
      Methods Enzymol. 1990;189:233-8. (PMID: 1963458)
      Clin Cancer Res. 1995 Jun;1(6):637-42. (PMID: 9816026)
      Biochim Biophys Acta. 2001 Feb 26;1530(2-3):146-54. (PMID: 11239817)
      Biochem Biophys Res Commun. 1997 Oct 9;239(1):80-4. (PMID: 9345273)
      J Biol Chem. 2010 May 14;285(20):15324-15332. (PMID: 20228061)
      FASEB J. 1996 Jul;10(9):993-1001. (PMID: 8801182)
      Mol Cell Biol. 2007 Feb;27(3):803-17. (PMID: 17101779)
      Mol Cell Biol. 1997 Mar;17(3):1552-61. (PMID: 9032283)
      J Biochem. 2005 Oct;138(4):493-500. (PMID: 16272145)
      Annu Rev Nutr. 2000;20:535-59. (PMID: 10940345)
      J Immunol. 2012 Jun 1;188(11):5593-603. (PMID: 22544925)
      Mol Cell Biol. 2007 Oct;27(19):6933-47. (PMID: 17646388)
      Life Sci. 1994;55(16):PL307-12. (PMID: 7934625)
      Arch Biochem Biophys. 1991 Nov 1;290(2):293-302. (PMID: 1656875)
      J Biol Chem. 1994 Feb 25;269(8):5913-7. (PMID: 7509793)
      J Cell Sci. 2009 Oct 15;122(Pt 20):3772-9. (PMID: 19812309)
      J Bioenerg Biomembr. 2004 Apr;36(2):211-7. (PMID: 15224971)
      Cell Mol Life Sci. 1999 Oct 30;56(5-6):538-42. (PMID: 11212303)
    • Accession Number:
      0 (Karyopherins)
      0 (PPAR gamma)
      0 (Receptors, Cytoplasmic and Nuclear)
      5688UTC01R (Tretinoin)
      EC 2.7.12.2 (MAP Kinase Kinase 1)
      EC 2.7.12.2 (Map2k1 protein, mouse)
    • Publication Date:
      Date Created: 20140625 Date Completed: 20151123 Latest Revision: 20231213
    • Publication Date:
      20231215
    • Accession Number:
      PMC4069188
    • Accession Number:
      10.1371/journal.pone.0100862
    • Accession Number:
      24959884