Stub1 Maintains Sox2 Protein Stability

The transcription factor SOX2 is a master regulator of embryonic-and induced pluripotent stem cells and its overexpression has been shown to involve in pathophysiology of cancers,fuels tumor initiation and contributes to tumor aggressiveness.The transcriptional activity of Sox2 has been extensively studied in both cancers and stem cells while its post-translational modification in terms of protein stability especially in cancers remains to be unexplored.Here,we show that Stub1,a U-box containing protein acts as an E3 ligase for maintaining Sox2 protein stability.Stub1 degrades Sox2 through polyubiquitination by forming ubiquitin lys33 chains on 245th lysine residue of Sox2.Thus,Stubl contributes to Sox2 homeostasis not only in cancers but also it ranges from normal cells to cancers stem cells,embryonic stem cells and induced pluripotent stem cells highlighting a general pathway for regulation of Sox2 protein expression.