PXD035882-1

PXD035882 is an original dataset announced via ProteomeXchange.

Title	Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes
Description	The involvement of G-Protein-Coupled Receptors’ (GPCR) location bias in diverse cellular functions and their misregulation in pathology is an underexplored territory. HCAR1, a GPCR for lactate is linked to cancer progression, mainly due to Warburg effect, but its mechanism of action remains elusive. Here, we show HCAR1 has a nuclear localization, capable of signaling intranuclearly to induce nuclear-ERK and AKT phosphorylation concomitant with higher cancer cell proliferation and survival. We determine its nuclear interactome, proving its involvement in protein-translation and DNA-damage repair. Nuclear HCAR1 (N-HCAR1) directly interacts with chromatin/DNA promoting expression of genes involved in cellular migration. Notably, we show N-HCAR1 particularly regulates a broader transcriptomic signature than its plasma membrane counterpart, emphasizing on the facts that functional output of N-HCAR1 is larger than plasma membrane localized HCAR1. Our study presents several unprecedented processes by which a GPCR through location-biased activity regulate various cellular functions and how cancer cells exploit these.
HostingRepository	PRIDE
AnnounceDate	2025-01-22
AnnouncementXML	Submission_2025-01-22_06:33:58.270.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD035882
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Eric Bonneil
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-08 09:48:52	ID requested
⏵ 1	2025-01-22 06:33:58	announced

10.6019/PXD035882;

submitter keyword: Signaling, Lactate,HCAR1, Location bias, Cancer, Warburg effect, Nucleus, GPCR

Sylvain Chemtob
contact affiliation	Program in Molecular Biology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
contact email	sylvain.chemtob@umontreal.ca
lab head
Eric Bonneil
contact affiliation	Proteomic Platform
contact email	eric.bonneil@umontreal.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035882
     1. Label: PRIDE project
     2. Name: Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes