FEBS Letters
Volume 583, Issue 12 , Pages 1846-1852, 18 June 2009

Interactions with LC3 and polyubiquitin chains link nbr1 to autophagic protein turnover

Edited by Noboru Mizushima

  • Sarah Waters

      Affiliations

    • King’s College London, Department of Medical and Molecular Genetics, London SE1 9RT, UK
    • King’s College London British Heart Foundation Centre of Research Excellence, The Randall Division for Cell and Molecular Biophysics and Cardiovascular Division, London SE1 1UL, UK
    • ,
  • Katie Marchbank

      Affiliations

    • King’s College London, Department of Medical and Molecular Genetics, London SE1 9RT, UK
    • ,
  • Ellen Solomon

      Affiliations

    • King’s College London, Department of Medical and Molecular Genetics, London SE1 9RT, UK
    • ,
  • Caroline Whitehouse

      Affiliations

    • King’s College London, Department of Medical and Molecular Genetics, London SE1 9RT, UK
    • ,
  • Mathias Gautel

      Affiliations

    • King’s College London British Heart Foundation Centre of Research Excellence, The Randall Division for Cell and Molecular Biophysics and Cardiovascular Division, London SE1 1UL, UK
    • Corresponding Author InformationCorresponding author. Fax: +44 207 848 6435.

Received 24 February 2009; received in revised form 18 April 2009; accepted 30 April 2009. published online 08 May 2009.

Abstract 

Nbr1, a ubiquitous kinase scaffold protein, contains a PB1, and a ubiquitin-associated (UBA) domain. We show here that the nbr1 UBA domain binds to lysine-48 and -63 linked polyubiquitin-B chains. Nbr1 also binds to the autophagic effector protein LC3-A via a novel binding site. Ubiquitin-binding, but not PB1-mediated p62/SQSTM1 interaction, is required to target nbr1 to LC3 and polyubiquitin-positive bodies. Nbr1 binds additionally to proteins implicated in ubiquitin-mediated protein turnover and vesicle trafficking: ubiquitin-specific peptidases USP8, and the endosomal transport regulator p14/Robld3. Nbr1 thus contributes to specific steps in protein turnover regulation disrupted in several hereditary human diseases.

Structured summary

MINT-7034452: USP8 (uniprotkb:P40818) physically interacts (MI:0218) with NBR1 (uniprotkb:Q14596) by pull down (MI:0096)

MINT-7034438: SQSTM1 (uniprotkb:Q13501) and LC3 (uniprotkb:Q9H492) colocalize (MI:0403) by fluorescence microscopy (MI:0416)

MINT-7034309: NBR1 (uniprotkb:Q14596) physically interacts (MI:0218) with Ubiquitin (uniprotkb:P62988) by pull down (MI:0096)

MINT-7034323: NBR1 (uniprotkb:P97432) physically interacts (MI:0218) with Ubiquitin (uniprotkb:P62988) by pull down (MI:0096)

MINT-7034233: NBR1 (uniprotkb:Q14596) physically interacts (MI:0218) with USP8 (uniprotkb:P40818) by two hybrid (MI:0018)

MINT-7034207: NBR1 (uniprotkb:Q14596) physically interacts (MI:0218) with Robld3 (uniprotkb:Q9JHS3) by two hybrid (MI:0018)

MINT-7034400, MINT-7034418: NBR1 (uniprotkb:Q14596) and LC3 (uniprotkb:Q9H492) colocalize (MI:0403) by fluorescence microscopy (MI:0416)

MINT-7034167: NBR1 (uniprotkb:Q14596) physically interacts (MI:0218) with Ubiquitin B (uniprotkb:Q78XY9) by two hybrid (MI:0018)

MINT-7034470: NBR1 (uniprotkb:Q14596) and USP8 (uniprotkb:P40818) colocalize (MI:0403) by fluorescence microscopy (MI:0416)

MINT-7034194: NBR1 (uniprotkb:Q14596) physically interacts (MI:0218) with LC3-A (uniprotkb:Q91VR7) by two hybrid (MI:0018)

MINT-7034336: SQSTM1 (uniprotkb:Q13501) physically interacts (MI:0218) with Ubiquitin (uniprotkb:P62988) by pull down (MI:0096)

MINT-7034375: NBR1 (uniprotkb:Q14596) physically interacts (MI:0218) with LC3 (uniprotkb:Q9H492) by pull down (MI:0096)

MINT-7034350: NBR1 (uniprotkb:Q14596) and Ubiquitin (uniprotkb:P62988) colocalize (MI:0403) by fluorescence microscopy (MI:0416)

MINT-7034181: NBR1 (uniprotkb:Q14596) physically interacts (MI:0218) with Tmed10 (uniprotkb:Q9D1D4) by two hybrid (MI:0018)

MINT-7034220: NBR1 (uniprotkb:Q14596) physically interacts (MI:0218) with ube2o (uniprotkb:Q6ZPJ3) by two hybrid (MI:0018)

Keywords: Nbr1, p62/SQSTM1, Ubiquitin, Vesicular transport, LC3, Autophagy, Myopathy

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PII: S0014-5793(09)00356-1

doi:10.1016/j.febslet.2009.04.049

FEBS Letters
Volume 583, Issue 12 , Pages 1846-1852, 18 June 2009

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