Int J Stem Cells.  2025 Nov;18(4):401-411. 10.15283/ijsc25023.

Kap1 Regulates Protein Stability of Nanog by Interfering with Fbxw8-Dependent Ubiquitination

• Moon HJ
• Lee N
• Lee BS
• Park MS
• Jung YJ
• Kim YS
• Kim JH

• KMID: 2574564
• DOI: http://doi.org/10.15283/ijsc25023

Abstract

Nanog is a key transcription factor that regulates the self-renewal and pluripotency of embryonic stem cells (ESCs). Although Kap1 has been demonstrated to regulate the stability of stemness factors, including Oct4 and Lin28A, its role in regulating Nanog protein stability in ESCs remains unexplored. In the present study, we examined the interaction between Kap1 and Nanog and its role in stabilizing the Nanog protein. Immunoprecipitation assays revealed that Nanog specifically interacted with the coiled-coil domain of Kap1. Kap1 overexpression increased the stability of the Nanog protein by inhibiting its ubiquitination and proteasomal degradation, whereas Kap1 silencing accelerated Nanog degradation. Furthermore, Kap1 overexpression inhibits Nanog degradation by interfering with the binding of Nanog to Fbxw8, an E3 ubiquitin ligase that promotes Nanog degradation via a proteasome-dependent process. These results indicate that Kap1 acts as a key regulator to preserve ESC properties by modulating the protein stability of stemness factors, including Oct4, Lin28A, and Nanog.

Keyword

Ubiquitin-protein ligase; Proteolysis; Protein stability; Ubiquitination; Embryonic stem cells