PXD041141-2

PXD041141 is an original dataset announced via ProteomeXchange.

Title	SETD5 regulates the OGT-catalyzed O-GlcNAcylation of RNA polymerase II, which is involved in the stemness of colorectal cancer cells
Description	The dosage-dependent recruitment of RNA polymerase II (Pol II) at the promoters of genes related to neurodevelopment and stem cell maintenance is required for transcription by the fine-tuned expression of SET-domain-containing protein 5 (SETD5). Pol II O-GlcNAcylation by O-GlcNAc transferase (OGT) is critical for preinitiation complex formation and transcription cycling. SETD5 dysregulation has been linked to stem cell-like properties in some cancer types; however, the role of SETD5 in cancer cell stemness has not yet been determined. We here show that aberrant SETD5 overexpression induces stemness in colorectal cancer (CRC) cells. SETD5 overexpression causes the upregulation of PI3K-AKT pathway-related genes and cancer stem cell (CSC) markers such as CD133, Kruppel-like factor 4 (KLF4), and estrogen-related receptor beta (ESRRB), leading to the gain of stem cell-like phenotypes. Our findings also revealed a functional relationship between SETD5, OGT, and Pol II. OGT-catalyzed Pol II glycosylation depends on SETD5, and the SETD5-Pol II interaction weakens in OGT-depleted cells, suggesting a SETD5-OGT-Pol II interdependence. SETD5 deficiency reduces Pol II occupancy at PI3K-AKT pathway-related genes and CD133 promoters, suggesting a role for SETD5-mediated Pol II recruitment in gene regulation. Moreover, the SETD5 depletion nullified the SETD5-induced stemness of CRC cells and Pol II O-GlcNAcylation. These findings support the hypothesis that SETD5 mediates OGT-catalyzed O-GlcNAcylation of RNA Pol II, which is involved in cancer cell stemness gain via CSC marker gene upregulation.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:14:31.675.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	HanByeol Kim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	O-(N-acetylamino)hexosyl-L-serine
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-27 19:08:42	ID requested
1	2023-11-15 16:26:36	announced
⏵ 2	2024-10-22 06:14:32	announced	2024-10-22: Updated project metadata.

10.1038/S41598-023-46923-1;

submitter keyword: O-GlcNAc, SETD5, colorectal cancer

Yeun Kyu Jang
contact affiliation	Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
contact email	ykjang@yonsei.ac.kr
lab head
HanByeol Kim
contact affiliation	Seoul nation University
contact email	existstar1@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041141
     1. Label: PRIDE project
     2. Name: SETD5 regulates the OGT-catalyzed O-GlcNAcylation of RNA polymerase II, which is involved in the stemness of colorectal cancer cells