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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

dTAG-Mediated Protein Degradation Dissects Nanog Function During ESC Differentiation

  1. 1Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia

Abstract

Protein degradation systems, such as auxin-inducible degron (AID) and dTAG-mediated degradation, have become essential tools in molecular biology. Their primary advantage lies in the rapid and efficient elimination of proteins, which facilitates the study of short-term molecular perturbations. However, these techniques remain underutilized for investigating protein function during the dynamic process of embryonic stem cell (ESC) differentiation. Here, we employed these methods to unveil the role of Nanog during definitive endoderm specification. We demonstrate that dTAG-inducible degradation is significantly more efficient than the AID system for Nanog elimination. Using this approach, we show that Nanog is a context-dependent regulator; while it maintains pluripotency in undifferentiated ESCs, it promotes definitive endoderm maturation during spontaneous differentiation. Our results highlight the advantages of targeted protein degradation for studying developmental transitions and provide new insights into the multifaceted functions of Nanog.

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BibTeX
@article{vasilin2026dtagmediated,
  title = {{dTAG-Mediated Protein Degradation Dissects Nanog Function During ESC Differentiation}},
  author = {Vladislav V. Vasilin and Anna S. Zinovyeva and Mikhail N. Gordeev and Ekaterina E. Petrenko and Anna S. Tsimokha and Nikolay D. Aksenov and Alexey N. Tomilin and Evgeny I. Bakhmet},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = nov,
  doi = {10.3390/ijms27219941},
  url = {https://www.mdpi.com/1422-0067/27/21/9941},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - dTAG-Mediated Protein Degradation Dissects Nanog Function During ESC Differentiation
AU  - Vladislav V. Vasilin
AU  - Anna S. Zinovyeva
AU  - Mikhail N. Gordeev
AU  - Ekaterina E. Petrenko
AU  - Anna S. Tsimokha
AU  - Nikolay D. Aksenov
AU  - Alexey N. Tomilin
AU  - Evgeny I. Bakhmet
PY  - 2026
DA  - 2026/11/06
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219941
UR  - https://www.mdpi.com/1422-0067/27/21/9941
AB  - Protein degradation systems, such as auxin-inducible degron (AID) and dTAG-mediated degradation, have become essential tools in molecular biology. Their primary advantage lies in the rapid and efficient elimination of proteins, which facilitates the study of short-term molecular perturbations. However, these techniques remain underutilized for investigating protein function during the dynamic process of embryonic stem cell (ESC) differentiation. Here, we employed these methods to unveil the role of Nanog during definitive endoderm specification. We demonstrate that dTAG-inducible degradation is significantly more efficient than the AID system for Nanog elimination. Using this approach, we show that Nanog is a context-dependent regulator; while it maintains pluripotency in undifferentiated ESCs, it promotes definitive endoderm maturation during spontaneous differentiation. Our results highlight the advantages of targeted protein degradation for studying developmental transitions and provide new insights into the multifaceted functions of Nanog.
SN  - 1422-0067
ER  -