PXD056341

PXD056341 is an original dataset announced via ProteomeXchange.

Title	A Molecular Glue of RBM39 and DCAF15 Arrests Cell Cycle Progression by Downregulation of CEP192
Description	RBM39 is a crucial component of the spliceosome that is critical for the integrity of mature mRNA, while depletion of RBM39 by Indisulam significantly increases RNA splicing defects. The antitumor activity of Indisulam is partially attributed to its inhibitory effects on cell cycle progression. To identify the key effector proteins responsible for cell cycle arrest following RBM39 depletion, we employed a multi-omics approach utilizing two chemotypes of RBM39 degraders: Indisulam and CB039. Through proteomics analysis, RNA sequencing, and DepMap cancer cell line dependency analysis, we identified CEP192 as a key gene that exhibited dependency in 96% of 1,100 cancer cell lines. In a panel of eight cancer cell lines, we observed consistent phenotypes upon treatment with CB039 and Indisulam, including skipping of CEP192 exon 42 and downregulation of the CEP192 protein. Mechanistically, treatment with CB039 and Indisulam, as well as CEP192 knockdown via RNA interference, resulted in arrest of cell cycle progression at the G2/M phase. This treatment also induced a disorganized spindle phenotype, as well as condensed and undivided chromosomes. In summary, this work enhances our understanding of the anti-mitotic mechanism underlying RBM39 molecular glue degraders.
HostingRepository	PRIDE
AnnounceDate	2025-03-20
AnnouncementXML	Submission_2025-03-20_06:22:19.491.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	He Huang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-28 01:46:32	ID requested
⏵ 1	2025-03-20 06:22:20	announced

10.1021/ACS.JMEDCHEM.5C00534;

submitter keyword: RBM39, CEP192, Indisulam, Proteomics Analysis, Cell Cycle Arrest

He Huang
contact affiliation	Chinese Academy of Sciences Shanghai Institute of Materia Medica
contact email	hhuang@simm.ac.cn
lab head
He Huang
contact affiliation	Shanghai Institute of Materia Medica
contact email	hhuang.nu@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056341
     1. Label: PRIDE project
     2. Name: A Molecular Glue of RBM39 and DCAF15 Arrests Cell Cycle Progression by Downregulation of CEP192