Dataset Information

LC-MS analysis of MPND associated complexes in H1299 cells

ABSTRACT: he Mpr1/Pad1 N-terminal domain-containing protein (MPND) belongs to the JAMM family of deubiquitinases and is ubiquitously expressed across human tissues. However, its role in non-small cell lung cancer (NSCLC) remains unexplored. In this study, we demonstrate that MPND expression is frequently reduced in NSCLC, and that low levels of MPND correlate with poor clinical outcomes. Depletion of MPND in vitro enhances cell migration, invasion, and cancer stem cell (CSC)-like characteristics in NSCLC cells. Mechanistically, MPND interacts with histones, removing ubiquitin from H2A K119 monoubiquitination (H2A K119ub) and H2B K120 monoubiquitination (H2B K120ub). Loss of MPND elevates these ubiquitination marks, leading to alterations in chromatin architecture. Furthermore, MPND influences gene transcription, and its depletion activates the TGF-beta/SMAD3 signaling pathway. Specifically, knockout of MPND increases H2B K120 ubiquitination and chromatin accessibility at the SMAD3 locus, facilitating its transcriptional activation. Using mouse tumor models and clinical samples from NSCLC patients, we show that loss of MPND triggers activation of the TGF-beta/SMAD3 axis, thereby promoting tumor growth and metastasis. Collectively, these findings deepen our understanding of the epigenetic mechanisms underlying NSCLC progression and suggest that anti-TGF-beta therapies may be particularly beneficial for treating MPND-deficient tumors.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell Of Lung

DISEASE(S): Lung Cancer

SUBMITTER: Dawei Li

LAB HEAD: Dawei Li

PROVIDER: PXD067575 | Pride | 2026-05-15

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 9

Similar Datasets

Project description:NguyenLK2011 - Ubiquitination dynamics in Ring1B-Bmi1 system This theoretical model investigates the dynamics of Ring1B/Bmi1 ubiquitination to identify bistable switch-like and oscillatory behaviour in the system. Michaelis-Menten (MM) equations are used to formulate the model. However, the authors show that the dynamics persist even for Mass-Action kinetics. This SBML file is the MM version of the model. This model is described in the article: Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system. Nguyen LK, Muñoz-García J, Maccario H, Ciechanover A, Kolch W, Kholodenko BN. PLoS Comput. Biol. 2011 Dec; 7(12): e1002317 Abstract: In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots and oscillations in Ring1B catalytic activity and proteosomal degradation are controlled by the abundances of Bmi1 and Ring1B, and the activities and abundances of external ligases and deubiquitinases, such as E6-AP and USP7. This model is hosted on BioModels Database and identified by: BIOMD0000000622. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

			Action	DRS
	MEI00108583-RZYXQ_F1.dat	Other
	MEI00108583-RZYXQ_F2.dat	Other
	MEI00108583_F1.raw	Raw
	MEI00108583_F2.raw	Raw
	MEI00108584-SXJ75_F1.dat	Other

Dataset Information

LC-MS analysis of MPND associated complexes in H1299 cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets