PXD050586

PXD050586 is an original dataset announced via ProteomeXchange.

Title	Mlf Mediates Proteotoxic Response via Formation of Cellular Foci for Protein Folding and Degradation
Description	Myeloid 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.
HostingRepository	PRIDE
AnnounceDate	2025-05-13
AnnouncementXML	Submission_2025-05-13_06:19:55.041.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pavel Talacko
SpeciesList	scientific name: Giardia intestinalis (Giardia lamblia); NCBI TaxID: 5741;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-13 06:40:28	ID requested
⏵ 1	2025-05-13 06:19:56	announced

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;

submitter keyword: : Myeloid leukemia factor, Giardia, protein quality control, ubiquitin-rich bodies, stress response, proteasome

Pavel Doležal
contact affiliation	Department of Parasitology, Faculty of Science, Charles University, BIOCEV, Prague, Czech Republic
contact email	pavel.dolezal@natur.cuni.cz
lab head
Pavel Talacko
contact affiliation	BIOCEV, Faculty of Science, Charles University in Prague
contact email	pavel.talacko@natur.cuni.cz
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050586
     1. Label: PRIDE project
     2. Name: Mlf Mediates Proteotoxic Response via Formation of Cellular Foci for Protein Folding and Degradation