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Silencing of the PHLDA1 leads to global proteome changes and differentiation pathways of human neuroblastoma cells

ABSTRACT: Neuroblastoma (NB) is the most common extracranial pediatric solid tumor originating from the abnormal development of cells of the sympathoadrenal lineage of the neural crest. Targeting GD2 ganglioside (GD2), a glycolipid expressed on neuroblastoma cells, with GD2 ganglioside-recognizing antibodies affects several pivotal signaling routes that drive or influence the malignant phenotype of the cells. Previously performed gene expression profiling helped us to identify the PHLDA1 (pleckstrin homology-like domain family A member 1) gene as the most upregulated gene in the IMR-32 human neuroblastoma cells treated with the mouse 14G2a monoclonal antibody. Mass spectrometry-based proteomic analyses were applied to better characterize a role of PHLDA1 protein in the response of neuroblastoma cells to chimeric ch14.18/CHO antibody. Additionally, global protein expression profile analysis in the IMR-32 cell line with PHLDA1 silencing revealed increase in biological functions of mitochondria, accompanied by differentiation-like phenotype of the cells. Moreover, mass spectrometry analysis of the proteins co-immunoprecipitated using anti-PHLDA1-specific antibody, selected a group of possible PHLDA1 binding partners. Also, a more detailed analysis suggested that PHLDA1 interacts with the DCAF7/AUTS2 complex, a key component of neuronal differentiation in vitro.

INSTRUMENT(S): Orbitrap Exploris 480, LTQ Orbitrap Elite, Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Agata Malinowska

LAB HEAD: Hanna Rokita

PROVIDER: PXD044319 | Pride | 2024-02-15

REPOSITORIES: Pride

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			Action	DRS
	00214217rok_PBSIgG.raw	Raw
	00214218rok_PBSPH.raw	Raw
	00214219rok_ABIgG.raw	Raw
	00214220rok_ABPH.raw	Raw
	00325475rok_PBSIgG.raw	Raw

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