PXD015157

PXD015157 is an original dataset announced via ProteomeXchange.

Title	Nuclear and cytosolic fractions of SOX2 synergise as transcriptional and translational co-regulators of cell fate
Description	Stemness depends on a series of specific transcription regulators that suppress default differentiation and/or promote self-renewal. A prominent example thereof is SOX2 (SRY homology Box 2), a protein that further contributes to pluripotency and the reprogramming of somatic cells to induced pluripotent stem cells (iPSCs). Here we uncover that SOX2 exerts these functions not only via transcriptional roles, but also by directly regulating translation. We show that SOX2 associates with ribosomal 40S subunits in the cytoplasm to alter the protein expression of signaling factors and metabolic components pivotal for stemness. Specifically, a low complexity region in the C-terminal part of SOX2 that interacts with the ribosome to modulate protein synthesis, is identified as critically required for SOX2-induced clonogenicity in human cancer cells and the reprogramming of fibroblasts to iPSCs. Mechanistically, SOX2 translationally enforces insulin/PI3K signaling while suppressing the formation of acetyl CoA synthetase 2 (ACSS2) protein, a driver of acetate consuming cell differentiation. Expression of either full-length SOX2 or its C-terminus only increases glucose consumption and acidification in cultured human cancer cells, thereby promoting clonogenicity. In the absence of SOX2 expression, ACSS2 knockdown or supplementation with acetate provide a partial rescue. Together, these data indicate novel ribosome-based mechanistic contributions of pluripotency factors to stemness and cell fate determination.
HostingRepository	PRIDE
AnnounceDate	2024-09-16
AnnouncementXML	Submission_2024-09-16_00:55:02.195.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD015157
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Thomas Bock
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation; Acetyl; Carbamidomethyl
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-27 02:23:59	ID requested
⏵ 1	2024-09-16 00:55:02	announced

10.6019/PXD015157;

curator keyword: Biological

submitter keyword: SOX2, Ribosome, Reprogramming, Stemness

Alexander Schmidt
contact affiliation	Proteomics Core Facility, Biozentrum, University of Basel, Spitalstrasse 41, CH-4056 Basel / Switzerland, Phone: +41 61 207 20 59, email: alex.schmidt@unibas.ch
contact email	alex.schmidt@unibas.ch
lab head
Thomas Bock
contact affiliation	Proteomics Core Facility, Biozentrum, University of Basel, Switzerland
contact email	thomas.bock@unibas.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015157
     1. Label: PRIDE project
     2. Name: Nuclear and cytosolic fractions of SOX2 synergise as transcriptional and translational co-regulators of cell fate