PXD031692

PXD031692 is an original dataset announced via ProteomeXchange.

Title	Mmp14 is essential for circadian clock rhythmicity in fibroblasts
Description	Membrane type I-matrix metalloproteinase (MT1-MMP/Mmp14) is an unusual MMP because it is essential for survival in mice with multiple organ systems being affected for reasons that are unclear. Here, we show that the protein (MT1-MMP) and gene (Mmp14) are under strict circadian clock control and conditional knockout in fibroblasts leads to ~16% of the proteome losing or inverting circadian rhythmicity. The result is loss of the actin cytoskeleton and cell-matrix adhesions and major imbalance of the matrisome. Lack of collagen-I monomer turnover results in excess fibril formation in the absence of Mmp14. In the absence of Mmp14, paired-like homeodomain transcription factor 2 (Pitx2) is upregulated and remains in the nucleus where it drives Plod2 expression. The overall result is accumulation of collagen fibrils and elevated pyridinoline crosslinking that renders collagen fibrils insoluble. In conclusion, Mmp14 is a master regulator of circadian rhythms affecting the actin cytoskeleton and cell microenvironment.
HostingRepository	PRIDE
AnnounceDate	2023-10-31
AnnouncementXML	Submission_2023-10-31_10:07:07.380.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	VenkateshMallikarjun
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-15 08:52:28	ID requested
⏵ 1	2023-10-31 10:07:07	announced

Dataset with its publication pending

submitter keyword: QE-HFX,MT1-MMP, circadian clock, tendon, mouse, chronomatrix, fibroblasts

Karl E.Kadler
contact affiliation	Professor of Biochemistry, University of Manchester, UK. Director, Wellcome Trust Centre for Cell-Matrix Research. Director, Cellular & Developmental Systems Domain, Faculty of Biology, Medicine and Health, University of Manchester
contact email	karl.kadler@manchester.ac.uk
lab head
VenkateshMallikarjun
contact affiliation	University of Manchester
contact email	vm9uq@virginia.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031692
     1. Label: PRIDE project
     2. Name: Mmp14 is essential for circadian clock rhythmicity in fibroblasts