PXD069033-1

PXD069033 is an original dataset announced via ProteomeXchange.

Title	Impact of PPP1R1A Knockdown on the Proteomic Landscape of INS-1 Cells: A Focus on Significant Modulated Pathways
Description	PPP1R1A, or protein phosphatase 1 regulatory inhibitor subunit 1A, is an essential regulatory protein that plays a pivotal role in various cellular processes, including metabolism, cell division, and signal transduction. This protein primarily functions as an inhibitor of protein phosphatase 1 (PP1), which is a major serine/threonine phosphatase responsible for the dephosphorylation of numerous substrates involved in critical signalling pathways [1]. By regulating PP1 activity, PPP1R1A influences diverse physiological functions, including muscle contraction, neuronal signalling, and insulin secretion. Dysregulation of PPP1R1A has been implicated in several diseases, including type 2 diabetes, cardiovascular diseases, and certain cancers, underscoring its significance in maintaining cellular homeostasis and overall metabolic health [2-5]. Due to its regulatory functions, PPP1R1A is a potential target for therapeutic interventions aimed at restoring normal cellular function in pathological conditions. Our previous research demonstrated that disruption of PPP1R1A in INS-1 cells led to decreased insulin secretion and impaired glucose uptake, accompanied by significant downregulation of key β-cell function genes including Ins1, Ins2, Pcsk1, Pdx1, Mafa, and components of the exocytosis and calcium transport machinery [6]. Importantly, cell viability, reactive oxygen species levels, apoptosis, and proliferation remained unaffected, indicating a specific impact on β-cell functional pathways. Additionally, we found that PPP1R1A expression is regulated by PDX1 and can be upregulated by rosiglitazone treatment. Building upon these findings, our current proteomics analysis serves as a continuation to further elucidate the molecular mechanisms by which PPP1R1A modulates β-cell function and insulin secretion. We examined downstream proteins involved in the affected signalling pathways identified in our proteomics analysis. These findings were subsequently validated by western blotting, which corroborated the alterations in key pathway components, thereby strengthening the evidence of PPP1R1A’s regulatory impact on β-cell molecular networks.
HostingRepository	PRIDE
AnnounceDate	2025-12-11
AnnouncementXML	Submission_2025-12-11_02:57:46.574.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexander Giddey
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: NEWT:10116;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-01 04:45:59	ID requested
⏵ 1	2025-12-11 02:57:47	announced

10.1021/ACS.JPROTEOME.5C00889;

submitter keyword: INS-1 cells,PPP1R1A, insulin secretion, type 2 diabetes, phosphorylation

Jalal Taneera
contact affiliation	College of Medicine, Department of Medical Sciences, University of Sharjah, Sharjah, UAE Center of Excellence of Precision Medicine, Sharjah Institute for Medical Research, Sharjah, UAE Research Institute of Medical and Research Sciences, Sharjah, UAE
contact email	jtaneera@sharjah.ac.ae
lab head
Alexander Giddey
contact affiliation	University of Cape Town
contact email	gddale001@myuct.ac.za
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/12/PXD069033

PRIDE project URI

• PRIDE
  1. PXD069033
     1. Label: PRIDE project
     2. Name: Impact of PPP1R1A Knockdown on the Proteomic Landscape of INS-1 Cells: A Focus on Significant Modulated Pathways