Hypothesis of functional sOGT regulation by O-GlcNAcylation. sOGT is O-GlcNAcylated at Thr12 and/or Ser56, which affects sOGT substrate selectivity. Expression of T12A results in less O-GlcNAcylation of HNRNPU and PDCD6IP as well as low abundance of CDC5L and, hence, reduces cell proliferation and causes G2/M cell cycle arrest. The O-GlcNAcylation loss would also elevate CUL1 abundance, hence promoting G1-to-S-phase transition. Expression of S56A enhances O-GlcNAcylation of HNRNPU and PDCD6IP, which may cause cell proliferation through unknown mechanisms.