PXD034270

PXD034270 is an original dataset announced via ProteomeXchange.

Title	O-GlcNAcylation Promotes Cerebellum Development and Medulloblastoma Oncogenesis via SHH Signaling
Description	Sonic hedgehog (Shh) signaling plays a critical role in regulating cerebellum development by maintaining the physiological proliferation of granule neuron precursors (GNPs), and its dysregulation leads to the oncogenesis of medulloblastoma. O-GlcNAcylation (O-GlcNAc) of proteins is an emerging regulator of brain function that maintains normal development and neuronal circuitry. Here, we demonstrate that O-GlcNAc transferase (OGT) in GNPs mediate the cerebellum development, and the progression of the Shh-subgroup of medulloblastoma. Specifically, OGT regulates the proliferation of GNPs by activating the Shh signaling pathway via O-GlcNAcylation at S355 of GLI family zinc finger 2 (Gli2), which in turn promotes its deacetylation and transcriptional activity via dissociation from p300, a histone acetyltransferases (HATs). Inhibition of OGT via genetic ablation or chemical inhibition improves survival in a medulloblastoma mouse model. These data uncover a critical role for O-GlcNAc signaling in cerebellar development, and pinpoint a potential therapeutic target for Shh-associated medulloblastoma.
HostingRepository	iProX
AnnounceDate	2022-06-02
AnnouncementXML	Submission_2022-09-27_20:55:55.923.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haitao Wu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	deamidated residue; acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-02 05:21:59	ID requested
1	2022-06-14 18:49:18	announced
⏵ 2	2022-09-27 20:55:56	announced	2022-09-28: Update publication information.

Chen L, Li Y, Song Z, Xue S, Liu F, Chang X, Wu Y, Duan X, Wu H, O-GlcNAcylation promotes cerebellum development and medulloblastoma oncogenesis via SHH signaling. Proc Natl Acad Sci U S A, 119(34):e2202821119(2022) [pubmed]

submitter keyword: O-GlcNAcylation, O-GlcNAc transferase, Sonic hedgehog

Haitao Wu
contact affiliation	Beijing Institute of Basic Medical Sciences
contact email	wuht@bmi.ac.cn
lab head
Haitao Wu
contact affiliation	Beijing Institute of Basic Medical Sciences
contact email	wuht@bmi.ac.cn
dataset submitter

iProX dataset URI