Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Temporal proteomics of p97/VCP inhibition

ABSTRACT: To facilitate the development of p97 inhibitors as potential therapeutic agents and help define their clinical application, it is necessary to dissect the mechanism of action (MOA) of p97 inhibitors and compare them with proteasome inhibitors. Moreover, identifying specific cellular markers is critical for both the drug discovery and development process, to help validate candidate drugs and quantify their effect. In this study, we performed proteomic analysis and systematically compared p97 shRNA knockdown (KD), and three p97 inhibitors, with the proteasome inhibitor MG132 in HCT116 colon cancer cells. Through proteomic analyses we uncover the specific molecular mechanism by which p97 inhibition is distinct from proteasome inhibition, potentially relevant to understanding the efficacious effects of the former in solid tumors.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Feng Wang

LAB HEAD: Feng Wang

PROVIDER: PXD025225 | Pride | 2021-12-15

REPOSITORIES: pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	19.raw	Raw
	20.raw	Raw
	21.raw	Raw
	22.raw	Raw
	23.raw	Raw

Items per page:

1 - 5 of 54

Publications

Temporal proteomics reveal specific cell cycle oncoprotein downregulation by p97/VCP inhibition.

Wang Feng F Li Shan S Houerbi Nadia N Chou Tsui-Fen TF

Cell chemical biology 20211129 3

Targeting protein quality control (PQC) pathways using proteasome or p97/VCP inhibition can effectively treat blood tumors. However, in solid tumors, only p97/VCP inhibitors are effective. To probe this difference in efficacy, we tracked HCT116 colon cancer cells using temporal proteomics to define the cellular and molecular responses to proteasome and p97 inhibition. Proteins involved in general PQC pathways were similarly upregulated by both treatments, suggesting that the proteotoxic stress c ...[more]

PMID: 34847375

Similar Datasets

Temporal proteomics of p97/VCP inhibition

Project description:To facilitate the development of p97 inhibitors as potential therapeutic agents and help define their clinical application, it is necessary to dissect the mechanism of action (MOA) of p97 inhibitors and compare them with proteasome inhibitors. Moreover, identifying specific cellular markers is critical for both the drug discovery and development process, to help validate candidate drugs and quantify their effect. In this study, we performed proteomic analysis and systematically compared p97 shRNA knockdown (KD), and three p97 inhibitors, with the proteasome inhibitor MG132 in HCT116 colon cancer cells. Through proteomic analyses we uncover the specific molecular mechanism by which p97 inhibition is distinct from proteasome inhibition, potentially relevant to understanding the efficacious effects of the former in solid tumors.

2021-12-15 | PXD025167 | Pride

Temporal proteomics of p97/VCP inhibition

2021-12-15 | PXD025094 | Pride

The ERAD inhibitor Eeyarestatin I is a bifunctional compound with an ER localizing domain and a p97/VCP inhibitory group

Project description:Protein homeostasis in the endoplasmic reticulum (ER) has recently emerged as a therapeutic target for cancer treatment. Disruption of ER homeostasis results in ER stress, which is a major cause of cell death for cells exposed to the proteasome inhibitor Bortezomib, an anti-cancer drug approved for treatment of multiple myeloma and Mantle cell lymphoma. We recently reported that the ERAD inhibitor Eeyarestatin I (EerI) also disturbs ER homeostasis and has anti-cancer activities resembling that of Bortezomib. Our findings reveal a class of bifunctional chemical agents that can preferentially inhibit membrane-bound p97 to disrupt ER homeostasis and induce tumor cell death. These results also suggest that the AAA ATPase p97 may be a potential drug target for cancer therapy. Cells were treated with EerI, CBU-028, or 5-NA each at 10uM in duplicates for 10h

2010-11-24 | E-GEOD-23849 | biostudies-arrayexpress

The ERAD inhibitor Eeyarestatin I is a bifunctional compound with an ER localizing domain and a p97/VCP inhibitory group

2010-11-24 | GSE23849 | GEO

The differentiation/retrodifferentiation program of human U937 leukemia cells is accompanied by changes of VCP/p97

Project description:A possible functional role of VCP/p97 during differentiation of U937 cells was addressed by siRNA-targeting of VCP/p97. Functional changes in VCP-siRNA-transfected cells following phorbol ester-induced monocytic differentiation have been examind by DNA microarray analysis. Cells transfected with the non-targeting AllStars negative siRNA (Qiagen) served as a reference. Computed

2010-06-29 | E-GEOD-9821 | biostudies-arrayexpress

The differentiation/retrodifferentiation program of human U937 leukemia cells is accompanied by changes of VCP/p97

2008-01-23 | GSE9821 | GEO

p97/VCP promotes the recycling of endocytic cargo

Project description:The endocytic pathway is of central importance for eukaryotic cells, as it enables uptake of extracellular materials, membrane protein quality control and recycling, as well as modulation of receptor signaling. While the ATPase p97 (VCP, Cdc48) has been found to be involved in the fusion of early endosomes and endolysosomal degradation, its role in endocytic trafficking is still incompletely characterized. Here, we identify myoferlin (MYOF), a ferlin family member with functions in membrane trafficking and repair, as a hitherto unknown p97 interactor. The interaction of MYOF with p97 depends on the cofactor PLAA previously linked to endosomal sorting. Besides PLAA, shared interactors of p97 and MYOF comprise several proteins involved in endosomal recycling pathways, including Rab11, Rab14 and the transferrin receptor CD71. Accordingly, a fraction of p97 and PLAA localizes to MYOF-, Rab11-, and Rab14-positive endosomal compartments. Pharmacological inhibition of p97 delays transferrin recycling, indicating that p97 promotes not only the lysosomal degradation, but also the recycling of endocytic cargo.

2023-09-28 | PXD041169 | Pride

Analysis of transcriptional changes associated to proteasome inhibition in HCT-116 human colorectal cancer cells

Project description:The proteasome is a central player in several cellular aspects, such as homeostasis, cell cycle progression, and even transcription. Recent work has shown that proteasome inhibition promotes pervasive epigenetic changes in the human genome. However, the impact of proteasome inhibitors on ncRNAs is poorly understood. We treated control (asynchronous) or G2-synchronized HCT-116 human colon cancer cells with the proteasome inhibitors MG132 and bortezomib and performed total RNA-seq. We also included cells treated simultaneously with MG132 and the RNA-pol II inhibitor α-amanitin to determine the transcriptional changes mediated by such RNA polymerase. We report that MG132 and bortezomib impact similar regions of the genome. A remarkable transcriptional activation was observed in centromeres and pericentromers, especially in α-satellite repeats. RNAs emanating from these regions are known to participate in chromosome segregation. Our results suggest that the proteasome can regulate mitotic progression, not only by participating in protein turnover, but also by regulating ncRNAs.

2021-12-14 | GSE165325 | GEO

Transcription profiling of human MCF-7 cells treated with proteasome inhibitor MG132 and either dexamethasone or 17b-estradiol

Project description:The objective of the study was to investigate the effect of proteasome inhibition on glucocorticoid and estrogen receptor regulated gene expression. Experiment Overall Design: MCF-7 cells were treated with proteasome inhibitor (MG132), dexamethasone, 17b-estradiol or MG132 plus dexamethasone or MG132 plus 7b-estardiol. Control cells were not treated. RNA was collected from 2 biological experiments.

2008-06-20 | E-GEOD-8383 | biostudies-arrayexpress

p97/VCP inhibition radiosensitises cancer cells through excessive MRE11-dependent DNA end resection

Project description:Cancer cells are under constant proteotoxic stress and have an increased genomic instability. They therefore rely on upregulation of protein homeostasis and the DNA damage response (DDR) for survival. The ubiquitin-dependent ATPase p97 is a central component of the ubiquitin-proteasome degradation system (UPS), involved in both protein homeostasis and DDR. p97 is overexpressed in many tumours and its overexpression correlates with poor prognosis in patients. To explore the concept of cancer cell killing by combined targeting of DDR and proteostasis, we induced DNA damage by ionising radiation (IR) and inhibited proteostasis by CB-5083, a specific small molecule inhibitor of p97, in bladder cancer cell lines and a mouse xenograft model. Combined therapy induced radiosensitivity and supressed xenograft tumour growth. Mechanistically, inactivation of the p97 ATPase activity results in proteotoxic accumulation of the nuclease MRE11 at the sites of IR-induced DNA lesions. This leads to excessive formation of single-stranded DNA (ssDNA), inhibition of HR, reliance on SSA for DSB repair and synthetic lethality after IR exposure in non-homologous end-joining-defective tumour cells such as those in muscle-invasive bladder carcinoma patients

2021-05-18 | PXD016279 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data