PXD061295

PXD061295 is an original dataset announced via ProteomeXchange.

Title	Affinity proteomics on PEX1 and PEX1-G843D in HCT116 Cells
Description	The PEX1/PEX6 AAA-ATPase is required for the biogenesis and maintenance of peroxisomes. Mutations in HsPEX1 and HsPEX6 disrupt peroxisomal matrix protein import and are the leading cause of Peroxisome Biogenesis Disorders (PBDs). The most common disease-causing mutation in PEX1 is the HsPEX1G843D allele, which results in a reduction of peroxisomal protein import. Here we demonstrate that in vitro the homologous yeast mutant, ScPex1G700D, reduces the stability of Pex1’s active D2 ATPase domain and impairs assembly with Pex6, but can still form an active AAA-ATPase motor. In vivo, ScPex1G700D exhibits only a slight defect in peroxisome import. We generated model human HsPEX1G843D cell lines and show that PEX1G843D is rapidly degraded by the proteasome, but that induced overexpression of PEX1G843D can restore peroxisome import. Additionally, we found that the G843D mutation reduces PEX1’s affinity for PEX6, and that impaired assembly is sufficient to induce degradation of PEX1WT. Lastly, we found that fusing a deubiquitinase to PEX1G843D significantly hinders its degradation in mammalian cells.
HostingRepository	PRIDE
AnnounceDate	2025-04-28
AnnouncementXML	Submission_2025-04-28_09:58:40.498.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD061295
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Connor Sheedy
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-27 19:17:28	ID requested
⏵ 1	2025-04-28 09:58:41	announced

Sheedy CJ, Chowdhury SP, Ali BA, Miyamoto J, Pang EZ, Bacal J, Tavasoli KU, Richardson CD, Gardner BM, remains functional in peroxisome biogenesis but is rapidly degraded by the proteasome. J Biol Chem, 301(5):108467(2025) [pubmed]

10.6019/PXD061295;

10.1016/j.jbc.2025.108467;

submitter keyword: Human, FLAG-affinity, HCT116, PEX1

Brooke Meghan Gardner
contact affiliation	Department of Molecular, Cellular, and Developmental Biology (MCDB) at University of California Santa Barbara (UCSB)
contact email	brookegardner@ucsb.edu
lab head
Connor Sheedy
contact affiliation	University of California Santa Barbara
contact email	connorsheedy@ucsb.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD061295
     1. Label: PRIDE project
     2. Name: Affinity proteomics on PEX1 and PEX1-G843D in HCT116 Cells