The Size of the Proteasomal Substrate Determines Whether Its Degradation Will Be Mediated by Mono- or Polyubiquitylation

Nitzan Shabek, Yifat Herman-Bachinsky, Samuel Buchsbaum, Oded Lewinson, Mahmood Haj-Yahya, Mirva Hejjaoui, Hilal A. Lashuel, Thomas Sommer, Ashraf Brik, Aaron Ciechanover

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90 Citations (Scopus)

Abstract

A polyubiquitin chain anchored to the substrate has been the hallmark of proteasomal recognition. However, the degradation signal appears to be more complex and to contain also a substrate's unstructured region. Recent reports have shown that the proteasome can degrade also monoubiquitylated proteins, which adds an additional layer of complexity to the signal. Here, we demonstrate that the size of the substrate is an important determinant in its extent of ubiquitylation: a single ubiquitin moiety fused to a tail of up to ~150 residues derived from either short artificial repeats or from naturally occurring proteins, is sufficient to target them for proteasomal degradation. Importantly, chemically synthesized adducts, where ubiquitin is attached to the substrate via a naturally occurring isopeptide bond, display similar characteristics. Taken together, these findings suggest that the ubiquitin proteasomal signal is adaptive, and is not always made of a long polyubiquitin chain.

Original languageEnglish
Pages (from-to)87-97
Number of pages11
JournalMolecular Cell
Volume48
Issue number1
DOIs
Publication statusPublished - 12 Oct 2012
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Shabek, N., Herman-Bachinsky, Y., Buchsbaum, S., Lewinson, O., Haj-Yahya, M., Hejjaoui, M., Lashuel, H. A., Sommer, T., Brik, A., & Ciechanover, A. (2012). The Size of the Proteasomal Substrate Determines Whether Its Degradation Will Be Mediated by Mono- or Polyubiquitylation. Molecular Cell, 48(1), 87-97. https://doi.org/10.1016/j.molcel.2012.07.011