PXD014707

PXD014707 is an original dataset announced via ProteomeXchange.

Title	Synthetic essentiality of metabolic regulator PDHK1 in PTEN-deficient cells and cancer
Description	PTEN is a tumor suppressor that is often inactivated in cancer and possesses both lipid and protein phosphatase activities. We report the metabolic regulator PDHK1 (pyruvate dehydrogenase kinase1) is a synthetic-essential gene in PTEN-deficient cancer and normal cells. The predominant mechanism of PDHK1 regulation and dependency is the PTEN protein phosphatase dephosphorylates NFkB activating protein (NKAP) and limits NFkB activation to suppress expression of PDHK1, a NFkB target gene. Loss of the PTEN protein phosphatase upregulates PDHK1 to drive aerobic glycolysis and induce PDHK1 cellular dependence. PTEN-deficient human tumors harbor increased PDHK1, which is a biomarker of decreased patient survival, establishing clinical relevance. This study uncovers a PTEN-regulated signaling pathway and reveals PDHK1 as a potential target in PTEN-deficient cancers.
HostingRepository	PRIDE
AnnounceDate	2019-09-11
AnnouncementXML	Submission_2019-09-11_10:29:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeffrey Johnson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-23 05:47:15	ID requested
⏵ 1	2019-09-11 10:29:42	announced

Chatterjee N, Pazarentzos E, Mayekar MK, Gui P, Allegakoen DV, Hrustanovic G, Olivas V, Lin L, Verschueren E, Johnson JR, Hofree M, Yan JJ, Newton BW, Dollen JV, Earnshaw CH, Flanagan J, Chan E, Asthana S, Ideker T, Wu W, Suzuki J, Barad BA, Kirichok Y, Fraser JS, Weiss WA, Krogan NJ, Tulpule A, Sabnis AJ, Bivona TG, Synthetic Essentiality of Metabolic Regulator PDHK1 in PTEN-Deficient Cells and Cancers. Cell Rep, 28(9):2317-2330.e8(2019) [pubmed]

submitter keyword: PTEN, protein phosphatase, PDHK1, NKAP, NFkB, synthetic lethality, metabolism, signaling, cancer

Trever Bivona
contact affiliation	Department of Medicine, University of California San Francisco, USA
contact email	trever.bivona@ucsf.edu
lab head
Jeffrey Johnson
contact affiliation	UCSF
contact email	jeffrey.johnson@ucsf.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014707
     1. Label: PRIDE project
     2. Name: Synthetic essentiality of metabolic regulator PDHK1 in PTEN-deficient cells and cancer