PXD015635

PXD015635 is an original dataset announced via ProteomeXchange.

Title	Identification of CDK1 phosphorylation of TFCP2L1 from murine embryonic stem cells and bladder cancer cells
Description	Molecular programs involved in embryogenesis are frequently upregulated in oncogenic dedifferentiation and metastasis. However, their precise roles and regulatory mechanisms remain elusive. Here, we showed that CDK1 phosphorylation of TFCP2L1, a pluripotency-associated transcription factor, orchestrated pluripotency and cell-cycling in embryonic stem cells (ESCs) and was aberrantly activated in aggressive bladder cancers (BCs). In murine ESCs, the protein interactome and transcription targets of Tfcp2l1 indicated its involvement in cell-cycle regulation. Tfcp2l1 was phosphorylated at Thr177 by Cdk1, which affected ESC cell-cycle progression, pluripotency, and differentiation. LC-MS was used to characterize thr177 phosphorylation in TFCP2L1 protein obtained by IP experiment and kinase assay. The CDK1-TFCP2L1 pathway was activated in human BC cells, stimulating their proliferation, self-renewal, and invasion. Lack of TFCP2L1 phosphorylation impaired the tumorigenic potency of BC cells in a xenograft model. In patients with BC, high co-expression of TFCP2L1 and CDK1 was associated with unfavorable clinical characteristics including tumor grade, lymphovascular and muscularis propria invasion, and distant metastasis and was an independent prognostic factor for cancer specific survival. These findings demonstrate the molecular and clinical significance of CDK1-mediated TFCP2L1 phosphorylation in stem-cell pluripotency and in the tumorigenic stemness features associated with BC progression.
HostingRepository	PRIDE
AnnounceDate	2019-11-08
AnnouncementXML	Submission_2019-11-08_08:42:58.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD015635
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Kyunggon Kim
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Ammonia-loss; Phospho; Cation:Na; Glu->pyro-Glu; Oxidation; Acetyl; Carbamidomethyl; Gln->pyro-Glu
Instrument	LTQ; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-30 01:42:38	ID requested
⏵ 1	2019-11-08 08:42:59	announced

Dataset with its publication pending

submitter keyword: Bladder cancer, CDK1, embryonic stem-cell, pluripotency, stemness features

Kyunggon Kim
contact affiliation	Asan Medical Center, Clinical Proteomics Core, Republic of Korea
contact email	kimkyunggon@gmail.com
lab head
Kyunggon Kim
contact affiliation	Asan Medical Center
contact email	kimkyunggon@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015635
     1. Label: PRIDE project
     2. Name: Identification of CDK1 phosphorylation of TFCP2L1 from murine embryonic stem cells and bladder cancer cells