PXD056593

PXD056593 is an original dataset announced via ProteomeXchange.

Title	Identification of ANXA1 as A Novel Upstream Negative Regulator of Notch1 Function in AML
Description	Abnormal Notch1 expression has an important role in tumorigenesis. However, upstream control mechanisms for Notch1 are still insufficiently understood. Acute myeloid leukemia (AML) is one of the most common and lethal blood malignancies with limited possibilities for treatment. Thus, new therapeutic targets are urgently needed to improve current ineffective therapies. Herein, we found high Annexin A1 (ANXA1) expression was corelated with hyperproliferation of AML cells, and then we identified ANXA1 as a novel negative regulator of Notch1 function in AML. Mechanistically, ANXA1 directly bound to the intracellular domain of Notch1 (NICD) to target this tumor suppressor for degradation. Furthermore, NICD executed its tumor suppressive function through activation of the p15 promoter. Thus, ablation of the Notch1-p15-mediated tumor suppression by ANXA1 provided a novel mechanism of AML proliferation. In human AML patients, we discovered a mutual exclusive relation existed between ANXA1 and Notch1/p15, corroborating our mechanistic discovery. On the basis of these results, we reasonably speculate that targeting ANXA1 would provide an effective approach for treatment of AML. In support of this new therapeutic paradigm, we provided proof-of-concept data by antagonizing ANXA1 using NICD inhibitory peptides.
HostingRepository	iProX
AnnounceDate	2024-10-03
AnnouncementXML	Submission_2024-10-08_01:03:52.371.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gang Shao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-08 01:03:36	ID requested
⏵ 1	2024-10-08 01:03:52	announced

Dataset with its publication pending

submitter keyword: Acute myeloid leukemia, Annexin A1, Notch1, Peptide inhibitors

Caiyun Fu
contact affiliation	Zhejiang Sci-Tech University
contact email	fucy03@126.com
lab head
Gang Shao
contact affiliation	Zhejiang Sci-Tech University
contact email	shaogangnyan@163.com
dataset submitter

iProX dataset URI