PXD040210

PXD040210 is an original dataset announced via ProteomeXchange.

Title	The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion
Description	Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent potentially lethal monogenic disorder. Mutations in the PKD1 gene, which encodes polycystin-1 (PC1), account for approximately 78% of cases. PC1 is a large 462-kDa protein that undergoes cleavage in its N and C-terminal domains. C-terminal cleavage produces fragments that translocate to mitochondria. We show that transgenic expression of a protein corresponding to the final 200 amino acid (aa) residues of PC1 in two Pkd1-KO orthologous murine models of ADPKD suppresses cystic phenotype and preserves renal function. This suppression depends upon an interaction between the C-terminal tail of PC1 and the mitochondrial enzyme Nicotinamide Nucleotide Transhydrogenase (NNT). This interaction modulates tubular/cyst cell proliferation, the metabolic profile, mitochondrial function, and the redox state. Together, these results suggest that a short fragment of PC1 is sufficient to suppress cystic phenotype and open the door to the exploration of gene therapy strategies for ADPKD.
HostingRepository	PRIDE
AnnounceDate	2023-02-17
AnnouncementXML	Submission_2023-02-17_12:26:05.619.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	TuKietLam
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidoethyl-L-cysteine; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-16 14:55:25	ID requested
⏵ 1	2023-02-17 12:26:05	announced

Dataset with its publication pending

submitter keyword: Metabolism, Polycystin-1 (PC1), C-terminal tail (CTT),Autosomal dominant polycystic kidney disease (ADPKD), Nicotinamide nucleotide transhydrogenase (NNT), mitochondria

TuKietLam
contact affiliation	Keck MS & Proteomics Resource Yale School of Medicine
contact email	tukiet.lam@yale.edu
lab head
TuKietLam
contact affiliation	Yale University
contact email	tukiet.lam@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040210
     1. Label: PRIDE project
     2. Name: The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion