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FAT10 and NUB1L bind to the VWA domain of Rpn10 and Rpn1 to enable proteasome-mediated proteolysis

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  • Neha Rani

    (University of Constance)

  • Annette Aichem

    (Biotechnology Institute Thurgau at the University of Constance)

  • Gunter Schmidtke

    (University of Constance)

  • Stefan G. Kreft

    (University of Constance)

  • Marcus Groettrup

    (University of Constance
    Biotechnology Institute Thurgau at the University of Constance)

Abstract

FAT10 is the only ubiquitin-like modifier that can target proteins for degradation by the proteasome in a ubiquitin-independent manner. The degradation of FAT10-linked proteins by the proteasome is strongly accelerated by the ubiquitin-like–ubiquitin-associated protein NEDD8 ultimate buster-1 long (NUB1L). Here we show how FAT10 and NUB1L dock with the 26S proteasome to initiate proteolysis. We identify the 26S proteasome subunit hRpn10/S5a as the receptor for FAT10, whereas NUB1L can bind to both Rpn10 and Rpn1/S2. Unexpectedly, FAT10 and NUB1L both interact with hRpn10 via the VWA domain. FAT10 degradation in yeast shows that human Rpn10 can functionally reconstitute Rpn10-deficient yeast and that the VWA domain of hRpn10 suffices to enable FAT10 degradation. Depletion of hRpn10 causes an accumulation of FAT10-conjugates also in human cells. In conclusion, we identify the VWA domain of hRpn10 as a receptor for ubiquitin-like proteins within the 26S proteasome and elucidate how FAT10 mediates efficient proteolysis by the proteasome.

Suggested Citation

  • Neha Rani & Annette Aichem & Gunter Schmidtke & Stefan G. Kreft & Marcus Groettrup, 2012. "FAT10 and NUB1L bind to the VWA domain of Rpn10 and Rpn1 to enable proteasome-mediated proteolysis," Nature Communications, Nature, vol. 3(1), pages 1-11, January.
  • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1752
    DOI: 10.1038/ncomms1752
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    1. Xiaojie Yan & Xinxin Yuan & Jianke Lv & Bing Zhang & Yongle Huang & Qianqian Li & Jinfeng Ma & Yanran Li & Xiaolu Wang & Yao Li & Ying Yu & Quanyan Liu & Tong Liu & Wenyi Mi & Cheng Dong, 2024. "Molecular basis of SAP05-mediated ubiquitin-independent proteasomal degradation of transcription factors," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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