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

Authors
 Yoojeong Seo  ;  Dong Keon Kim  ;  Jihye Park  ;  Soo Jung Park  ;  Jae Jun Park  ;  Jae Hee Cheon  ;  Tae Il Kim 
Citation
 CANCERS, Vol.16(5) : 1035, 2024-03 
Journal Title
CANCERS
Issue Date
2024-03
Keywords
Colorectal Cancer (CRC) ; O-GlcNAcylation ; Sox2 ; acetylation ; histone deacetylase (HDAC) ; post-translational modification (PTM)
Abstract
Aberrant expression of the pluripotency-associated transcription factor Sox2 is associated with poor prognosis in colorectal cancer (CRC). We investigated the regulatory roles of major post-translational modifications in Sox2 using two CRC cell lines, SW480 and SW620, derived from the same patient but with low and high Sox2 expression, respectively. Acetylation of K75 in the Sox2 nuclear export signal was relatively increased in SW480 cells and promotes Sox2 nucleocytoplasmic shuttling and proteasomal degradation of Sox2. LC-MS-based proteomics analysis identified HDAC4 and p300 as binding partners involved in the acetylation-mediated control of Sox2 expression in the nucleus. Sox2 K75 acetylation is mediated by the acetyltransferase activity of CBP/p300 and ACSS3. In SW620 cells, HDAC4 deacetylates K75 and is regulated by miR29a. O-GlcNAcylation on S246, in addition to K75 acetylation, also regulates Sox2 stability. These findings provide insights into the regulation of Sox2 through multiple post-translational modifications and pathways in CRC.
Files in This Item:
T202402187.pdf Download
DOI
10.3390/cancers16051035
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Keon(김동건)
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Park, Soo Jung(박수정)
Park, Jae Jun(박재준)
Park, Ji Hye(박지혜)
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198878
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