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PXD050586

PXD050586 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMlf Mediates Proteotoxic Response via Formation of Cellular Foci for Protein Folding and Degradation
DescriptionMyeloid leukemia factor 1 (Mlf1) was identified as a proto-oncoprotein that affects hematopoietic differentiation in humans. However, its cellular function remains elusive, spanning roles from cell cycle regulation to modulation of protein aggregate formation and participation in ciliogenesis. Given that structurally conserved homologs of Mlf1 can be found across the eukaryotic tree of life, we decided to characterize its cellular role underlying this phenotypic pleiotropy. Using a model of the unicellular eukaryote Giardia intestinalis, we demonstrate that its Mlf1 homolog (GiMlf) mainly localizes to two types of cytosolic foci: microtubule nucleation zones, where it interacts with Hsp40, and ubiquitin-rich, membraneless compartments, found adjacent to mitochondrion-related organelles known as mitosomes, containing the 26S proteasome regulatory subunit 4. Upon cellular stress, GiMlf either relocates to the affected compartment or disperses across the cytoplasm, subsequently accumulating into enlarged foci during the recovery phase. In vitro assays suggest that GiMlf can be recruited to membranes through its affinity for signaling phospholipids. Importantly, cytosolic foci diminish in the gimlf knockout strain, which exhibits extensive proteomic changes indicative of compromised proteostasis. Consistent with data from other cellular systems, we propose that Mlf acts in the response to proteotoxic stress by mediating the formation of function-specific foci for protein folding and degradation.
HostingRepositoryPRIDE
AnnounceDate2025-05-13
AnnouncementXMLSubmission_2025-05-13_06:19:55.041.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPavel Talacko
SpeciesList scientific name: Giardia intestinalis (Giardia lamblia); NCBI TaxID: 5741;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-03-13 06:40:28ID requested
12025-05-13 06:19:56announced
Publication List
Vinopalov, á M, Arbonov, á L, F, ü, ssy Z, Dohn, á, lek V, Samad A, B, í, l, ý T, Vancov, á M, Dole, ž, al P, Mlf mediates proteotoxic response via formation of cellular foci for protein folding and degradation in Giardia. PLoS Pathog, 20(10):e1012617(2024) [pubmed]
10.1371/journal.ppat.1012617;
Keyword List
submitter keyword: : Myeloid leukemia factor, Giardia, protein quality control, ubiquitin-rich bodies, stress response, proteasome
Contact List
Pavel Doležal
contact affiliationDepartment of Parasitology, Faculty of Science, Charles University, BIOCEV, Prague, Czech Republic
contact emailpavel.dolezal@natur.cuni.cz
lab head
Pavel Talacko
contact affiliationBIOCEV, Faculty of Science, Charles University in Prague
contact emailpavel.talacko@natur.cuni.cz
dataset submitter
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