PXD012340-2

PXD012340 is an original dataset announced via ProteomeXchange.

Title	CDK5RAP3, a UFL1 substrate adaptor, is critical for liver development
Description	Protein modification by ubiquitin and ubiquitin-like proteins (UBLs) regulates numerous biological functions. The UFM1 system, a novel UBL conjugation system, is implicated in mouse development and hematopoiesis. However, its broad biological functions and working mechanisms remain largely elusive. CDK5RAP3, a possible ufmylation substrate, is essential for epiboly and gastrulation in zebrafish. Herein, we report a crucial role of CDK5RAP3 in liver development and hepatic functions. Cdk5rap3 knockout mice displayed prenatal lethality with severe liver hypoplasia, as characterized by delayed proliferation and compromised differentiation. Hepatocyte-specific Cdk5rap3 knockout mice suffered post-weaning lethality, owing to serious hypoglycemia and impaired lipid metabolism. Depletion of CDK5RAP3 triggered endoplasmic reticulum stress and activated unfolded protein responses in hepatocytes. We detected the in vivo interaction of CDK5RAP3 with UFL1, the defined E3 ligase in ufmylation. Notably, loss of CDK5RAP3 altered the ufmylation profile in liver cells, suggesting that CDK5RAP3 serves as a novel substrate adaptor for this UBL modification. Collectively, our study identifies CDK5RAP3 as an important regulator of ufmylation and suggests the involvement of ufmylation in mammalian development.
HostingRepository	iProX
AnnounceDate	2019-01-14
AnnouncementXML	Submission_2020-09-03_21:16:18.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Weidi Xiao
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-14 23:35:49	ID requested
1	2019-01-14 23:39:16	announced
⏵ 2	2020-09-03 21:16:19	announced	2020-09-04: Update publication information

Yang R, Wang H, Kang B, Chen B, Shi Y, Yang S, Sun L, Liu Y, Xiao W, Zhang T, Yang J, Zhang Y, Zhu M, Xu P, Chang Y, Jia Y, Huang Y, CDK5RAP3, a UFL1 substrate adaptor, is crucial for liver development. Development, 146(2):(2019) [pubmed]

submitter keyword: Liver development, Ubiquitin-like proteins, Knockout mouse, Cdk5rap3, TMT labeling

Ping Xu
contact affiliation	State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Lifeomics, Beijing , China
contact email	xuping_bprc@126.com
lab head
Weidi Xiao
contact affiliation	Beijing Proteome Research Center
contact email	weidixiao@126.com
dataset submitter

iProX dataset URI