Dataset Information

Identification of vitamin K-dependent proteins in mouse liver by LC-MS/MS

ABSTRACT: Vitamin K (VK), a fat-soluble vitamin, functions as a co-factor during the gamma-carboxylation reaction that converts glutamic acid residues to gamma-carboxyglutamic acid residues in proteins transiting through the endoplasmic reticulum. Two enzymes are involved which together form the VK cycle: gamma-glutamyl carboxylase (GGCX), and vitamin K oxidoreductase (VKORC1). GGCX requires reduced VK (VKH2) as an essential cofactor, which upon carboxylation, is oxidized to VK epoxide and then reconverted to VKH2 by VKORC1. Physiologically, gamma-carboxylation is essential in the liver for the activity of several coagulation factors (e.g., prothrombin, factor IX, etc.), and in arteries and cartilage to modulate the activity of Matrix Gla Protein (MGP) which prevents extra-osseous tissue mineralization. Gamma-carboxylation also negatively regulates the function of osteocalcin, a bone-derived hormone that promotes glucose homeostasis. Our objective is to identify unrecognized gamma-carboxylated proteins.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Hepatocyte, Liver

SUBMITTER: Denis Faubert

LAB HEAD: Mathieu Ferron

PROVIDER: PXD032920 | Pride | 2023-05-10

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	OF_20180321_FER_01.mzid.gz	Mzid
	OF_20180321_FER_01.mzid_OF_20180321_FER_01.MGF	Mzid
	OF_20180321_FER_01.raw	Raw
	OF_20180321_FER_02.mzid.gz	Mzid
	OF_20180321_FER_02.mzid_OF_20180321_FER_02.MGF	Mzid

Items per page:

1 - 5 of 13

Similar Datasets

Project description:Glucocorticoids are an essential component of the treatment of lymphoid malignancies and resistance to glucocorticoid therapy constitutes a prominent clinical problem in relapsed and refractory lymphoblastic leukemias. Constitutively active NOTCH signaling is involved in the pathogenesis of over 50% of T-cell lymphoblastic leukemia (T-ALL) which harbor activating mutations in the NOTCH1 gene. Aberrant NOTCH1 signaling has been shown to protect normal thymocytes from glucocorticoid induced cell death. Here we analyzed the interaction of glucocorticoid therapy with inhibition of NOTCH signaling in the treatment of T-ALL. Gamma-secretase inhibitors (GSI), which block the activation of NOTCH receptors, amplified the transcriptional changes induced by glucocorticoid treatment, including glucocorticoid receptor autoinduction and restored sensitivity to dexamethasone in glucocorticoid-resistant T-ALL cells. Apoptosis induction upon inhibition of NOTCH signaling and activation of the glucocorticoid receptor was dependent on transcriptional upregulation of BIM and subsequent activation of the mitochondrial/intrinsic cell death pathway. Finally, we used a mouse xenograft model of T-ALL to demonstrate that combined treatment with dexamethasone and a GSI results in improved antileukemic effects in vivo. These studies provide insight in the mechanisms of glucocorticoid resistance and serve as rationale for the use of glucocorticoid and GSIs in combination in the treatment of T-ALL. Experiment Overall Design: Duplicate samples (biologic replicas) from CUTLL1 cells were treated for 24 hours with vehicle only (DMSO), dexamethasone (1microM), a gamma-secretase inhibitor (CompE 100nM) and a combination of dexamethasome plus gamma secretase inhibitor at the same concentrations indicated before. Gene expression profiling was analyzed to identify gene expression signatures assocuated with glucocorticoid treatment (dexamethasone), inhibition of NOTCH1 by gamma secretase inhibitor (CompE) or the combination of both treatments.

Dataset Information

Identification of vitamin K-dependent proteins in mouse liver by LC-MS/MS

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets