PXD026434

PXD026434 is an original dataset announced via ProteomeXchange.

Title	Pyruvate kinase M2 controls lipid homeostasis via regulation of SREBPs activation and intestinal cholesterol absorption
Description	The pyruvate kinase M2 isoform (PKM2) is preferentially expressed in cancer to regulate anabolic metabolism. However, the metabolic requirements of PKM2 in tumorigenesis have yielded contradictory results. Herein we discovered that this glycolytic enzyme regulates lipid homeostasis in cancer cell autonomous manner and at systemic levels. Transmembrane protein 33 (TMEM33) was identified as a downstream effector of PKM2, whose expression level positively correlates with plasma total cholesterol level in vivo. Loss of PKM2 leads to up-regulation of TMEM33, which recruits ring finger protein 5 (RNF5) to promote SCAP ubiquitination and degradation, thereby inhibiting Golgi translocation and activation of sterol regulatory element binding protein 1 (SREBP1). Moreover, global PKM2 knockout promoted allografted tumor growth, at least partially attributes to the elevated plasma cholesterol level caused by increased intestinal Niemann-Pick C1-Like 1 (NPC1L1) to facilitate cholesterol absorption. Collectively, PKM2-TMEM33 axis modulates cell autonomous lipid metabolism by regulating SREBP activation. PKM2 in small intestine plays critical functions in controlling systemic cholesterol level. Overall, our results underscore unappreciated functions of PKM2 in lipid homeostasis and imply that combining an allosteric activator of PKM2 with NPC1L1 inhibitor represents a therapeutic invention for cancer treatment.
HostingRepository	PRIDE
AnnounceDate	2021-08-06
AnnouncementXML	Submission_2021-08-06_10:36:35.217.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Min Ma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-02 15:24:53	ID requested
⏵ 1	2021-08-06 10:36:35	announced

Dataset with its publication pending

submitter keyword: PKM2,lipid, Human,LC-MS/MS

lingjun Li
contact affiliation	School of Pharmacy, UW madiosn
contact email	lingjun.li@wisc.edu
lab head
Min Ma
contact affiliation	UW madison
contact email	mma58@wisc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026434
     1. Label: PRIDE project
     2. Name: Pyruvate kinase M2 controls lipid homeostasis via regulation of SREBPs activation and intestinal cholesterol absorption