PXD027798-1

PXD027798 is an original dataset announced via ProteomeXchange.

Title	Rack1 is Essential for Corticogenesis by Preventing P21-Dependent Senescence in Neural Stem Cells
Description	Normal neurodevelopment relies on intricate signaling pathways that balance neural stem cell (NSC) self-renewal, maturation and survival. Disruptions lead to neurodevelopmental disorders including microcephaly. Here, we implicate the inhibition of NSC senescence as a mechanism underlying neurogenesis and corticogenesis. We report that the receptor for activated C kinase (Rack1), a family member of WD40-repeat (WDR) proteins, is highly enriched in NSCs. Deletion of Rack1 in developing cortical progenitors leads to a microcephaly phenotype. Strikingly, the absence of Rack1 decreases neurogenesis and promotes a cellular senescence phenotype in NSCs. Mechanistically, the senescence-related p21 signaling pathway is dramatically activated in Rack1-null NSCs, and removal of p21 significantly rescues the Rack1-knockout phenotype in vivo. Finally, Rack1 directly interacts with Smad3 to suppress the activation of TGF-β/Smad signaling pathway, which plays a critical role in p21-mediated senescence. Our data implicate Rack1-driven inhibition of p21-induced NSC senescence as a critical mechanism behind normal cortical development.
HostingRepository	iProX
AnnounceDate	2021-08-09
AnnouncementXML	Submission_2021-08-09_02:48:01.384.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haitao Wu
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-09 02:30:35	ID requested
⏵ 1	2021-08-09 02:48:01	announced

Dataset with its publication pending

submitter keyword: microcephaly, Rack1, neural stem cells, cellular senescence, p21, TGF-β/Smad

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