PXD007790

PXD007790 is an original dataset announced via ProteomeXchange.

Title	NAD Salvage Supports Serine Biosynthesis
Description	Maintenance of NAD+ levels by mitochondrial complex I, the NAD+ salvage pathway, and other routes is an important factor in of neurodegenerative disease and cancer. Both the production of NAD+ and the metabolic enzymes that require it as a redox cofactor or substrate differ widely in abundance across cell types and conditions. Disruption in the NAD+ supply thus exerts different effects depending on the cellular NAD+ requirements existing in the cell. Pharmacological depletion of NAD+ is actively being pursued in cancer and other diseases but these effects are not fully understood. Here, we combine quantitative proteomics and metabolomics to understand the consequences of disrupting cellular NAD+ levels and find that inhibiting the NAD+ salvage pathway depletes serine biosynthesis from glucose by impeding the NAD+-dependent protein 3-phosphoglycerate dehydrogenase (PHGDH). Importantly, breast cancers that depend on PHGDH are exquisitely sensitive to blocking the NAD+ salvage pathway. PHGDH, and the rate-limiting enzyme of NAD+ salvage are also correlated in public tumor proteome and transcript datasets. These findings are immediately translatable to the pharmacological inhibition of NAMPT in PHGDH-dependent cancers.
HostingRepository	PRIDE
AnnounceDate	2018-08-14
AnnouncementXML	Submission_2018-09-03_03:13:18.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD007790
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Patrick Murphy
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex; Oxidation; Carbamidomethyl
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-19 03:42:11	ID requested
1	2018-08-14 03:27:44	announced
⏵ 2	2018-09-03 03:13:19	announced	Updated publication reference for PubMed record(s): 30157431.

Murphy JP, Giacomantonio MA, Paulo JA, Everley RA, Kennedy BE, Pathak GP, Clements DR, Kim Y, Dai C, Sharif T, Gygi SP, Gujar S, Salvage Pathway Supports PHGDH-Driven Serine Biosynthesis. Cell Rep, 24(9):2381-2391.e5(2018) [pubmed]

curator keyword: Biological

submitter keyword: Serine, Complex I, NAD, FK866

Shashi Gujar
contact affiliation	Dalhousie University
contact email	shashi.gujar@dal.ca
lab head
Patrick Murphy
contact affiliation	Mass Spectrometry
contact email	pitter9@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007790
     1. Label: PRIDE project
     2. Name: NAD Salvage Supports Serine Biosynthesis