Dataset Information

ThBD-AGIA-AirID expressing MM1.S cells treated with DMSO, Pomalidomide or ARV-825

ABSTRACT: MM1.S cells stably expressing ThBD-AGIA-AirID were treated with DMSO, Pomalidomide or ARV-825 with MG132 in three biological replicates. Cell lysates were subjected to methanol-chloroform precipitation and digested with trypsin. Biotinylated peptides were purified by Tamavidin 2-REV and identified by LC-MS/MS analysis.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Hidetaka Kosako

PROVIDER: PXD067142 | JPOST Repository | Wed Sep 03 00:00:00 BST 2025

REPOSITORIES: jPOST

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	101_PJ1028_Yamada_5_MM1S_TAA_Pom_Tama_FusionIT.raw	Raw
	103_PJ1028_Yamada_8_MM1S_TAA_ARV825_Tama_FusionIT.raw	Raw
	105_PJ1028_Yamada_3_MM1S_TAA_DMSO_Tama_FusionIT.raw	Raw
	107_PJ1028_Yamada_6_MM1S_TAA_Pom_Tama_FusionIT.raw	Raw
	109_PJ1028_Yamada_9_MM1S_TAA_ARV825_Tama_FusionIT.raw	Raw

Items per page:

1 - 5 of 10

Publications

In-cell proximity target validation methods for heterobifunctional molecules with CRBN- or VHL-binder using AirID.

Yamada Kohdai K Yamanaka Satoshi S Yamakoshi Hiroyuki H Kohyama Aki A Iwabuchi Yoshiharu Y Kosako Hidetaka H Sawasaki Tatsuya T

Communications biology 20250830 1

Heterobifunctional molecules, such as proteolysis-targeting and autophagy-targeting chimera, represent new drug concepts. They are composed of two protein binders that can induce proximity interactions between two proteins and protein catalysis. Currently, cereblon (CRBN)- and von Hippel-Lindau (VHL)-binders with thalidomide- and VH032-backbones are widely used as E3 ligase binders. Here, we developed a method to validate proteins that interact with heterobifunctional molecules in cells using Ai ...[more]

PMID: 40885760

Similar Datasets

Project description:Background: Senescent hepatocytes accumulate in parallel with fibrosis progression during NASH. The mechanisms that enable progressive expansion of nonreplicating cell populations and the significance of that process in determining NASH outcomes are unclear. Many types of senescing cells upregulate the THBD-PAR-1 signaling axis to remain viable. Vorapaxar, an FDA-approved PAR-1 inhibitor, blocks the activity of that pathway. We used vorapaxar to determine if and how THBD-PAR1 signaling promotes fibrosis progression in NASH. Methods: We evaluated the THBD-PAR1 pathway in liver biopsies from NAFLD patient cohorts with a spectrum of liver fibrosis. Chow fed mice were treated with viral vectors to over-express p16 specifically in hepatocytes and induce replicative senescence. Effects on the THBD-PAR-1 axis and regenerative capacity were assessed; the transcriptome of p16 over-expressing hepatocytes was characterized and we examined how conditioned medium from senescent but viable (dubbed ‘undead’) hepatocytes reprograms hepatic stellate cells. A genetically obese mouse model of NASH with little liver fibrosis, and a diet-induced mouse model of NASH with advanced fibrosis were treated with vorapaxar to determine effects on hepatocyte senescence and liver damage. Results: Inducing senescence up-regulates the THBD-PAR1 signaling axis in hepatocytes and induces their expression of fibrogenic factors, including hedgehog ligands. Hepatocyte THBD-PAR1 signaling increases in NAFLD and supports sustained hepatocyte senescence that limits effective liver regeneration and promotes maladaptive repair. Inhibiting PAR-1 signaling with vorapaxar interrupts this process, reduces the burden of ‘undead’ senescent cells, and safely improves NASH and fibrosis despite ongoing lipotoxic stress Conclusion: The THBD-PAR1 signaling axis is a novel therapeutic target for NASH because blocking this pathway prevents accumulation of senescing but viable hepatocytes that generate factors that promote maladaptive liver repair.