A Comprehensive Understanding of Post-Translational Modification of Sox2 via Acetylation and O-GlcNAcylation in...

Area of Science:

• Molecular Biology
• Cancer Research
• Biochemistry

Background:

• Aberrant expression of Sox2, a pluripotency factor, correlates with poor prognosis in colorectal cancer (CRC).
• Sox2 regulation is complex and influenced by various cellular mechanisms.

Purpose of the Study:

• To investigate the regulatory roles of post-translational modifications (PTMs) on Sox2 in CRC.
• To elucidate the pathways controlling Sox2 stability and expression in different CRC cell lines.

Main Methods:

• Utilized two CRC cell lines (SW480 and SW620) with differing Sox2 expression levels.
• Employed Liquid Chromatography-Mass Spectrometry (LC-MS) based proteomics.
• Analyzed acetylation and O-GlcNAcylation modifications on Sox2.

Main Results:

• K75 acetylation in SW480 cells promotes Sox2 nuclear export and degradation, involving HDAC4 and p300.
• CBP/p300 and ACSS3 mediate Sox2 K75 acetylation, while HDAC4 (regulated by miR29a) deacetylates it in SW620 cells.
• S246 O-GlcNAcylation, alongside K75 acetylation, influences Sox2 stability.

Conclusions:

• Sox2 stability and expression in CRC are regulated by a network of PTMs, including acetylation and O-GlcNAcylation.
• These findings highlight novel regulatory pathways for Sox2, offering potential therapeutic strategies for colorectal cancer.