PXD023317

PXD023317 is an original dataset announced via ProteomeXchange.

Title	SUMOylation disassembles the tetrameric pyruvate kinase M2 to block myeloid differentiation of leukemia cells
Description	Leukemia arises from blockage of the differentiation/maturation of hematopoietic progenitor cells at different stages with uncontrolled proliferation of leukemic cells. However, the signal pathways that block cell differentiation remain unclear. Herein we found that SUMOylation of the M2 isoform of pyruvate kinase(PKM2), a rate-limiting glycolytic enzyme catalyzing the dephosphorylation of phosphoenolpyruvate to pyruvate, is prevalent in a variety of leukemic cell lines as well as primary samples from patients with leukemia through multiple-reaction monitoring based targeted mass spectrometry analysis. SUMOylation of PKM2 lysine 270(K270) triggered conformation change from tetrameric to dimeric of PKM2, reduced PK activity, and led to nuclear translocation of PKM2. SUMO1 modification of PKM2 recruits and promotes degradation of RUNX1 via a SUMO-interacting motif, resulting in blockage of myeloid differentiation of NB4 and U937 leukemia cells. Replacement of wild type PKM2 with a SUMOylation-deficient mutant (K270R) abrogated the interaction with RUNX1 and the blockage of myeloid differentiation in vitro and in xenograft model. Our results establish PKM2 as an essential modulator of leukemia cell differentiation and a potential therapeutic target which may offer synergistic effect with differentiation therapy in the treatment of leukemia.
HostingRepository	iProX
AnnounceDate	2020-12-26
AnnouncementXML	Submission_2022-11-15_21:01:11.483.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Li Xia
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-25 20:59:43	ID requested
⏵ 1	2022-11-15 21:01:12	announced

Xia L, Jiang Y, Zhang XH, Wang XR, Wei R, Qin K, Lu Y, SUMOylation disassembles the tetrameric pyruvate kinase M2 to block myeloid differentiation of leukemia cells. Cell Death Dis, 12(1):101(2021) [pubmed]

submitter keyword: SUMOylation, pyruvate kinase, differentiation, RUNX1

Ying Lu
contact affiliation	Shanghai Jiao Tong University School of Medicine
contact email	stove@shsmu.edu.cn
lab head
Li Xia
contact affiliation	Shanghai Jiao Tong University School of Medicine
contact email	lixia@shsmu.edu.cn
dataset submitter

iProX dataset URI