The ubiquitin-specific protease USP8 deubiquitinates and stabilizes Cx43.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Protein Processing, Post-Translational*; Breast Neoplasms/*pathology ; Connexin 43/*metabolism ; Endopeptidases/*metabolism ; Endosomal Sorting Complexes Required for Transport/*metabolism ; Ubiquitin/*metabolism ; Ubiquitin Thiolesterase/*metabolism; Autophagy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Cell Communication ; Connexin 43/genetics ; Endopeptidases/genetics ; Endosomal Sorting Complexes Required for Transport/genetics ; Female ; Humans ; Tumor Cells, Cultured ; Ubiquitin Thiolesterase/genetics ; Ubiquitination
    • Abstract:
      Connexin-43 (Cx43, also known as GJA1) is the most ubiquitously expressed connexin isoform in mammalian tissues. It forms intercellular gap junction (GJ) channels, enabling adjacent cells to communicate both electrically and metabolically. Cx43 is a short-lived protein which can be quickly degraded by the ubiquitin-dependent proteasomal, endolysosomal, and autophagosomal pathways. Here, we report that the ubiquitin-specific peptidase 8 (USP8) interacts with and deubiquitinates Cx43. USP8 reduces both multiple monoubiquitination and polyubiquitination of Cx43 to prevent autophagy-mediated degradation. Consistently, knockdown of USP8 results in decreased Cx43 protein levels in cultured cells and suppresses intercellular communication, revealed by the dye transfer assay. In human breast cancer specimens, the expression levels of USP8 and Cx43 proteins are positively correlated. Taken together, these results identified USP8 as a crucial and bona fide deubiquitinating enzyme involved in autophagy-mediated degradation of Cx43.
      (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)
    • References:
      EMBO J. 1998 Jun 15;17 (12 ):3241-50. (PMID: 9628861)
      Cell Res. 2015 Mar;25(3):306-17. (PMID: 25675982)
      Nat Med. 2011 Jun;17(6):708-14. (PMID: 21572428)
      Proc Natl Acad Sci U S A. 2016 Aug 9;113(32):E4688-97. (PMID: 27444016)
      EMBO J. 2014 Nov 3;33(21):2473-91. (PMID: 25216678)
      FEBS Lett. 2014 Apr 17;588(8):1221-9. (PMID: 24486527)
      J Biol Chem. 2016 Jul 22;291(30):15753-66. (PMID: 27302062)
      J Biol Chem. 1995 Nov 3;270(44):26399-403. (PMID: 7592854)
      Nat Rev Cancer. 2016 Dec;16(12 ):775-788. (PMID: 27782134)
      Mol Biol Cell. 2009 Jul;20(14):3342-52. (PMID: 19458184)
      Cell Adhes Commun. 2000;7(6):501-12. (PMID: 11051460)
      Exp Cell Res. 2009 Dec 10;315 (20):3587-97. (PMID: 19835873)
      Mol Cell Biol. 2007 Jul;27(13):5029-39. (PMID: 17452457)
      J Proteome Res. 2012 Dec 7;11(12 ):6134-46. (PMID: 23106098)
      Nat Rev Mol Cell Biol. 2009 Aug;10(8):550-63. (PMID: 19626045)
      J Membr Biol. 2007 Jun;217(1-3):43-51. (PMID: 17657522)
      Mol Biol Cell. 2007 Feb;18(2):337-47. (PMID: 17108328)
      Mol Biol Cell. 2012 Jun;23 (11):2156-69. (PMID: 22496425)
      Biochim Biophys Acta. 2016 Apr;1865(2):133-46. (PMID: 26855059)
      Trends Cell Biol. 2010 Feb;20(2):92-101. (PMID: 19944606)
      Biochem Soc Trans. 2006 Nov;34(Pt 5):754-6. (PMID: 17052190)
      J Cell Sci. 2017 Sep 1;130(17 ):2867-2882. (PMID: 28733455)
      Biol Cell. 2015 Jul;107(7):218-31. (PMID: 25818265)
      Physiol Rev. 2003 Oct;83(4):1359-400. (PMID: 14506308)
      Autophagy. 2012 May 1;8(5):794-811. (PMID: 22635056)
      Science. 2007 Jan 12;315(5809):201-5. (PMID: 17218518)
      Biochim Biophys Acta. 2012 Aug;1818(8):1870-9. (PMID: 21996040)
      J Biol Chem. 2010 Dec 24;285(52):40979-90. (PMID: 20940304)
      Cell Commun Adhes. 2003 Jul-Dec;10(4-6):173-80. (PMID: 14681012)
      Mol Cell. 2009 May 15;34(3):259-69. (PMID: 19450525)
      Cancer Lett. 2016 Apr 28;374(1):117-126. (PMID: 26884256)
      J Mol Cell Cardiol. 2015 Nov;88:1-13. (PMID: 26386426)
      Annu Rev Biochem. 1996;65:475-502. (PMID: 8811187)
      FASEB J. 2014 Nov;28(11):4629-41. (PMID: 25070368)
      Nat Genet. 2015 Jan;47(1):31-8. (PMID: 25485838)
      Physiol Rev. 2002 Apr;82(2):373-428. (PMID: 11917093)
      PLoS Biol. 2012 Jan;10 (1):e1001239. (PMID: 22253574)
      Biochem J. 2006 Mar 15;394(Pt 3):527-43. (PMID: 16492141)
      J Biol Chem. 2004 Nov 26;279(48):50089-96. (PMID: 15371442)
      J Cell Sci. 2004 Mar 1;117(Pt 7):1211-20. (PMID: 14970263)
    • Contributed Indexing:
      Keywords: Cx43; USP8; autophagy; connexin; degradation; deubiquitylation (deubiquitination); ubiquitin; ubiquitin ligase; ubiquitylation (ubiquitination)
    • Accession Number:
      0 (Connexin 43)
      0 (Endosomal Sorting Complexes Required for Transport)
      0 (GJA1 protein, human)
      0 (Ubiquitin)
      EC 3.4.- (Endopeptidases)
      EC 3.4.19.12 (USP8 protein, human)
      EC 3.4.19.12 (Ubiquitin Thiolesterase)
    • Publication Date:
      Date Created: 20180408 Date Completed: 20190122 Latest Revision: 20210317
    • Publication Date:
      20240829
    • Accession Number:
      PMC5971442
    • Accession Number:
      10.1074/jbc.RA117.001315
    • Accession Number:
      29626091