PXD031095

PXD031095 is an original dataset announced via ProteomeXchange.

Title	O-GlcNAcylation stabilizes ULK1 by inhibiting chaperone-mediated autophagy upon HPV infection
Description	Human papillomaviruses (HPVs) are conducive to a fraction of head and neck squamous cell carcinoma (HNSCC). Previously we demonstrated that HPV16 oncogene E6 or E6/E7 transduction increases the abundance of O-linked GlcNAcylation (O-GlcNAc) transferase (OGT). Herein we focus on the effects of O-GlcNAcylation on HPV-positive HNSCCs. We found that upon HPV infection, ULK1, an autophagy-initiating kinase, is hyper-O-GlcNAcylated, stabilized and linked with autophagy elevation. Through mass spectrometry, we identified that ULK1 is O-GlcNAcylated at Ser409Ser410, which is distinct from previously reported Thr635Thr754. It has been known that PKCαmediates phosphorylation of ULK1 at Ser423, which attenuates its stability by shunting ULK1 to the chaperon-mediated autophagy (CMA) pathway. By biochemical assays, we demonstrate that ULK1 Ser409Ser410 O-GlcNAcylation antagonizes its phosphorylation at pSer423. Mutations of Ser409ASer410A (2A) render ULK1 less stable by promoting interaction with the CMA chaperon Hsc70. Moreover, ULK1-2A mutants attenuate the association of ULK1 with STX17, which is vital for the fusion between autophagosomes and lysosomes. Analysis of the TCGA database reveals that ULK1 is upregulated in HPV-positive HNSCCs and its protein level positively correlates with HNSCC patient survival. Our work demonstrates that O-GlcNAcylation of ULK1 alters to reciprocate to the environmental changes. O-GlcNAcylation of ULK1 at Ser409Ser410 stabilizes ULK1, and it might underlie the molecular mechanism of HPV-positive HNSCC patient survival.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:27:33.616.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ke Qin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	O-(N-acetylamino)glucosyl-L-threonine; O-(N-acetylamino)glucosyl-L-serine
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-19 09:34:58	ID requested
1	2022-10-14 11:06:17	announced
⏵ 2	2023-11-14 07:27:37	announced	2023-11-14: Updated project metadata.

Shi Y, Yan S, Shao GC, Wang J, Jian YP, Liu B, Yuan Y, Qin K, Nai S, Huang X, Wang Y, Chen Z, Chen X, Dong MQ, Geng Y, Xu ZX, Li J, O-GlcNAcylation stabilizes the autophagy-initiating kinase ULK1 by inhibiting chaperone-mediated autophagy upon HPV infection. J Biol Chem, 298(9):102341(2022) [pubmed]

submitter keyword: O-GlcNAc

ULK1

HPV

HNSCC

Macroautophagy

Chaperone-mediated autophagy

Jing Li
contact affiliation	Beijing Key Laboratory of DNA Damage Response and College of Life Science, Capital Normal University, Beijing 100048, China
contact email	jing_li@cnu.edu.cn
lab head
Ke Qin
contact affiliation	Peking University
contact email	qinke@pku.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031095
     1. Label: PRIDE project
     2. Name: O-GlcNAcylation stabilizes ULK1 by inhibiting chaperone-mediated autophagy upon HPV infection