Dataset Information

Novel, highly potent PROTACs targeting AURORA-A kinase

ABSTRACT: The family of AURORA kinases is essential for cell cycle progression and dysregulation of AURORA-A in cancer led to a large number of clinical and pre-clinical inhibitors. However, ATP competitive AURORA-A inhibitors usually do not target non-catalytic functions that have also been identified as mechanisms promoting tumorigenesis. To target non-catalytic as well as catalytic functions, we developed a series of PROTACs (PROteolysis targeting chimeras) based on the selective AURORA-A kinase inhibitor MK-5108 (VX-689) and the CEREBLON E3-ligase ligands. The most potent PROTAC, JB301, had good physicochemical properties and cell penetration resulting in degradation of AURORA-A in leukemic cells at single digit nM concentration. In the presented datasets, we determined the intracellular degradation specificity of the AURKA PROTAC JB300. We therefore treated MV4-11 cells with JB300 and the corresponding ligand MK-5108, or DMSO and quantified the induced degradation using a label free approach.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Suspension Culture, Macrophage

DISEASE(S): Acute Leukemia

SUBMITTER: Nicola Berner

LAB HEAD: Bernhard Kuster

PROVIDER: PXD033239 | Pride | 2023-09-14

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20200824_swissprot_human_ci.fasta	Fasta
	5257_RF10_P060090_R1.raw	Raw
	5257_RF11_P060091_R1.raw	Raw
	5257_RF12_P060092_R1.raw	Raw
	5257_RF1_P060081_R1.raw	Raw

Items per page:

1 - 5 of 19

Similar Datasets

Project description:The majority of cell surface and secreted proteins are modified by glycans and this glycosylation process plays an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signalling. Glycosylation plays an important role in myogenesis and the development of muscle tissue but our molecular understanding of the precise glycans, catalytic enzymes and lectins involved remain only partially understood. Here, we quantified dynamic remodeling of the membrane-associated proteome during in vitro myogenesis. We observed wide-spread changes in the abundance of several receptors and important enzymes regulating glycosylation. Quantification of released N-linked glycans via glycomic analysis confirmed remodeling of the glycome with a switch in sialic acid linkages, and changes in di-galactosylation and paucimannosylation. Quantitative glycoproteomic analysis with stable isotope labelling, enrichment of glycopeptides and analysis via multiple fragmentation approaches identified precise glycoproteins containing these regulated glycans including integrins and growth factor receptors. Myogenesis was also associated with the regulation of several lectins including the up-regulation of Galectin-1 (LGALS1). CRISPR/Cas9-mediated deletion of Lgals1 inhibited differentiation and myotube formation suggesting an early defect in the myogenic program. We also observed similar changes in N-glycosylation and the up-regulation of LGALS1 during postnatal skeletal muscle development in mice. Finally, treatment of new-born mice with recombinant adeno-associated viruses to express LGALS1 in the musculature resulted in enhanced muscle mass. Our data will be a valuable resource to further understand the role of glycosylation and lectins on myogenesis and may aid in the development of intervention strategies aimed at promoting healthy muscle.

Dataset Information

Novel, highly potent PROTACs targeting AURORA-A kinase

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets