An IMiD-induced SALL4 degron system for selective degradation of target proteins

Commun Biol. 2020 Sep 18;3(1):515. doi: 10.1038/s42003-020-01240-5.


Regulating the amount of proteins in living cells is a powerful approach for understanding the functions of the proteins. Immunomodulatory drugs (IMiDs) induce the degradation of neosubstrates by interacting with celebron (CRBN) in the cullin E3 ubiquitin ligase complex (CRL4CRBN). Here, we developed the IMiD-dependent Sal-like protein 4 (SALL4) degron (S4D) system for chemical protein knockdown. In transient assays, an N- or C-terminal S4D tag induced the degradation of proteins localized to various subcellular compartments, including the plasma membrane. The activity of luciferase-S4D was reduced by 90% within 3 h of IMiD treatment. IMiD treatment reduced the expression of endogenous S4D-fused RelA and IκBα in knock-in (KI) experiments. Interestingly, the IκBα knockdown suggested that there may be another, unknown mechanism for RelA translocation to the nucleus. Furthermore, 5-hydroxythalidomide as a thalidomide metabolite specifically degradated S4D-tagged protein. These results indicate that the S4D system is a useful tool for cellular biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / genetics
  • Cell Membrane / immunology
  • Gene Knockdown Techniques / methods
  • HeLa Cells
  • Humans
  • Immunologic Factors / genetics*
  • Immunologic Factors / immunology
  • Immunologic Factors / pharmacology
  • Proteolysis*
  • Substrate Specificity
  • Thalidomide / analogs & derivatives
  • Thalidomide / immunology
  • Thalidomide / metabolism*
  • Thalidomide / pharmacology
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / immunology
  • Transcription Factors / genetics*
  • Transcription Factors / immunology
  • Transcriptional Elongation Factors / genetics
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / immunology


  • Elp1 protein, human
  • IL17RB protein, human
  • Immunologic Factors
  • RELA protein, human
  • SALL4 protein, human
  • Transcription Factor RelA
  • Transcription Factors
  • Transcriptional Elongation Factors
  • 5-hydroxythalidomide
  • Thalidomide
  • Ubiquitin-Protein Ligases