PXD064782

PXD064782 is an original dataset announced via ProteomeXchange.

Title	O-GlcNAcylation of the tumor suppressor LATS1 drives mitotic progression via PLK1
Description	Initially discovered in Drosophila, the Hippo pathway is pivotal for tissue growth and organ homeostasis. Regulated by both extrinsic and intrinsic signals, the Hippo pathway exerts its effect via a core kinase cascade, in which Large tumor suppressor 1 and 2 (LATS1/2) plays a key role. LATS1 has been shown to regulate mitotic progression by phosphorylate myosin phosphatase target subunit 1 (MYPT1) to counteract polo-like kinase (PLK1) activity, a mitotic master kinase. Herein we demonstrate that the hexosamine biosynthetic pathway regulates the Hippo pathway via LATS1. We show that LATS1 interacts with the O-GlcNAc transferase (OGT) and is O-GlcNAcylated. Via electron transfer dissociation mass spectrometry, we mapped the O-GlcNAcylation sites to be Ser479/Ser482/Thr484/Thr485. O-GlcNAcylation attenuates LATS1 protein stability, and downregulates the phosphorylation level of its downstream substrates, such MYPT1. Subsequently, decreased MYPT1-pS473 levels enhanced PLK1-pT210 levels and drives mitosis. Importantly, we demonstrate that in Drosophila O-GlcNAcylation of LATS1 promotes the fly wing size. Thus, this study suggests that O-GlcNAcylation links extrinsic glucose levels to LAST1 in the Hippo pathway and cell proliferation.
HostingRepository	PRIDE
AnnounceDate	2026-01-23
AnnouncementXML	Submission_2026-01-23_01:18:37.632.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD064782
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Wen Zhou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-09 06:43:07	ID requested
⏵ 1	2026-01-23 01:18:38	announced

Meng L, Wang Y, Zhou W, Wu S, Li J, O-GlcNAcylation of the tumor suppressor LATS1 drives mitotic progression via PLK1. J Biol Chem, 302(1):110990(2026) [pubmed]

10.6019/PXD064782;

10.1016/j.jbc.2025.110990;

submitter keyword: LATS1

Hippo

OGT

O-GlcNAc

PLK1

Wen Zhou
contact affiliation	Peking University
contact email	wen.zhou@pku.edu.cn
lab head
Wen Zhou
contact affiliation	Peking University
contact email	wen.zhou@pku.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064782
     1. Label: PRIDE project
     2. Name: O-GlcNAcylation of the tumor suppressor LATS1 drives mitotic progression via PLK1