PXD015790

PXD015790 is an original dataset announced via ProteomeXchange.

Title	Prolyl Hydroxylase Substrate Adenylosuccinate Lyase Is An 2 Oncogenic Driver In Triple Negative Breast Cancer
Description	Protein hydroxylation extensively regulates cellular signaling by affecting protein stability, activity, and interactome, therefore contributing to the pathogenesis of various diseases including cancers. However, because of the transient nature of the hydroxylase-substrate interaction, identifying new prolyl hydroxylation substrates remains a daunting challenge. Here, by developing a novel enzyme-substrate trapping strategy coupled with TAP-TAG or orthogonal GST- purification followed by mass spectrometry, we identify Adenylosuccinate lyase (ADSL) as a bona fide EglN2 prolyl hydroxylase substrate in triple negative breast cancer (TNBC). ADSL expression is significantly higher in TNBC than other breast cancer subtypes or normal breast tissues. Functionally, ADSL knockout greatly impairs TNBC 2-D and 3-D cell proliferation and invasiveness in vitro, as well as TNBC tumorigenesis and lung colonization in xenograft models. Mechanistically, an integrated transcriptomics and metabolomics analysis revealed that ADSL promotes the activation of the oncogenic cMYC pathway by regulating cMYC protein level via a mechanism requiring ADSL hydroxylation on proline 24. Specifically, hydroxylation-proficient ADSL, by affecting adenosine levels, represses the expression of the long non-coding RNA MIR22HG, thus upregulating the oncogene cMYC protein level and its target gene expression. Our findings identify the critical role of ADSL hydroxylation in controlling cMYC and TNBC tumorigenesis.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:05:24.999.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ling Xie
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-11 01:18:09	ID requested
1	2019-11-20 07:05:20	announced
2	2019-11-27 06:53:15	announced	2019-11-27: Updated project metadata.
⏵ 3	2024-10-22 04:05:25	announced	2024-10-22: Updated project metadata.

10.1038/s41467-019-13168-4;

Zurlo G, Liu X, Takada M, Fan C, Simon JM, Ptacek TS, Rodriguez J, von Kriegsheim A, Liu J, Locasale JW, Robinson A, Zhang J, Holler JM, Kim B, Zik, á, nov, á M, Bierau J, Xie L, Chen X, Li M, Perou CM, Zhang Q, Prolyl hydroxylase substrate adenylosuccinate lyase is an oncogenic driver in triple negative breast cancer. Nat Commun, 10(1):5177(2019) [pubmed]

submitter keyword: EglN2 prolyl hydroxylase,Protein hydroxylation, Adenylosuccinate lyase (ADSL)

Qing Zhang
contact affiliation	Department of Pathology UT Southwestern Medical Center
contact email	Qing.Zhang@UTSouthwestern.edu
lab head
Ling Xie
contact affiliation	UNC at Chapel Hill
contact email	xiel@email.unc.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/11/PXD015790

PRIDE project URI

• PRIDE
  1. PXD015790
     1. Label: PRIDE project
     2. Name: Prolyl Hydroxylase Substrate Adenylosuccinate Lyase Is An 2 Oncogenic Driver In Triple Negative Breast Cancer