SOX2 protein biochemistry in stemness, reprogramming, and cancer: the PI3K/AKT/SOX2 axis and beyond

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• The transcription factor SOX2 is crucial for cell fate determination during development, cellular reprogramming, and cancer progression.
• While SOX2's functions are widely studied, the post-translational modifications (PTMs) that regulate its activity remain under-explored.
• These PTMs are critical for fine-tuning SOX2's role in response to cellular demands.

Purpose of the Study:

• To comprehensively review the current knowledge on SOX2 protein modifications.
• To explore the relationship between SOX2 PTMs and the PI3K/AKT signaling pathway.
• To elucidate how these modifications impact SOX2's functions in stemness, reprogramming, and cancer.

Main Methods:

• Literature review of scientific reports on SOX2.
• Analysis of studies detailing SOX2 protein modifications.
• Examination of research linking SOX2 to the PI3K/AKT pathway.

Main Results:

• SOX2 undergoes diverse PTMs, including phosphorylation, methylation, acetylation, ubiquitination, SUMOylation, PARPylation, and O-glycosylation.
• These modifications are often heterogeneous, reciprocal, and can be tissue- and species-specific.
• A recurring regulatory theme involves the PI3K/AKT signaling axis, influencing SOX2 activity.

Conclusions:

• SOX2 PTMs are essential regulators of its biological functions.
• Understanding SOX2 modifications and their interplay with signaling pathways like PI3K/AKT is key to deciphering its roles in stemness, reprogramming, and cancer.
• Further research into these biochemical processes is warranted.