Protein modification and functional implications for Oct-4 in human stem cells.

Ishtiaq Ahmad; Evelyne Walker Nasir; Ahmad Khurshid; Saleem M.  Rafik; Nasir-Uddin; Daniel C.  Hoessli; Saleem M Rafik; Abdul Rauf Shakoori

A number of nuclear and cytosolic proteins have been identified that are modified by certain dynamic post-translational modifications by addition of O-GIcNAc (O-link N-acetylglucoseamine) and phosphate. These modifications play an important role in modulating their functions. Majority of transcriptional factors have been found to be modified by O-GIcNAc and these modifications are transitory with phosphate. Octamer binding protein-4 (Oct-4), an embryonic stem cell marker, was originally identified as a DNA-binding protein that activates gene transcription via a cis-element containing octamer motif. It is one of the POU transcription factors. Its expression has been observed in totipotent embryonic stem and germ cells. A critical level of Oct-4 expression is required to sustain stem cell self-renewal and pluripotency. Differentiation of embryonic stem cells results in down- regulation of Oct-4, an event essential for a proper and divergent developmental program. It is being proposed that post-translational modifications including O-GlcNAc addition and phosphate addition along with their interplay play a vital role in multiple switches of silencing of certain genes and activation of other genes in same or different cells resulting in specific differentiation of a cell.