PXD054152-1

PXD054152 is an original dataset announced via ProteomeXchange.

Title	Proteasome-dependent protein degradation shapes developmental tempo in mouse and human neural progenitors
Description	underlying molecular mechanisms remain poorly understood. To investigate the basis for species-specific developmental tempos, we performed a comprehensive comparative analysis of protein dynamics in mouse and human neural progenitors (NPs). Through a combination of targeted protein labelling, quantitative mass spectrometry, and functional genomics, we demonstrate that protein degradation is a key driver of tempo differences between mouse and human NPs. We observe a systematic 1.5-fold increase in protein half-lives in human NPs compared to mouse, independent of cellular compartment or protein function. This difference persists in post-mitotic neurons, indicating active degradation as the primary mechanism. Proteasomal activity is also ~1.5-fold higher in mouse NPs, consistent with upregulation of proteasome-associated proteins. Importantly, increasing the rate of proteolytic degradation of a key transcriptional repressor in neural progenitors accelerates the expression of its target gene and the rate of neuronal differentiation. Despite differences in degradation rates, protein synthesis rates are similar between species, resulting in higher protein content in human NPs. Our findings highlight the central role of protein degradation in controlling developmental tempo and provide insight into the molecular basis of evolutionary changes in developmental timing across species.
HostingRepository	PRIDE
AnnounceDate	2026-07-15
AnnouncementXML	Submission_2026-07-15_08:07:51.854.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Skehel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-23 11:05:32	ID requested
⏵ 1	2026-07-15 08:07:52	announced

Dataset with its publication pending

submitter keyword: Human, neural progenitor, degradation, mouse, proteasome, lc-ms/ms

James Briscoe
contact affiliation	Developmental Dynamics Lab, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT
contact email	James.Briscoe@crick.ac.uk
lab head
Mark Skehel
contact affiliation	Francis Crick Institute
contact email	skehelm@crick.ac.uk
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/2026/07/PXD054152

PRIDE project URI

• PRIDE
  1. PXD054152
     1. Label: PRIDE project
     2. Name: Proteasome-dependent protein degradation shapes developmental tempo in mouse and human neural progenitors