PXD036104

PXD036104 is an original dataset announced via ProteomeXchange.

Title	Acute pharmacological degradation of ERK5 does not inhibit cellular immune response or proliferation
Description	Over the past few decades, interest in the role that extracellular signal-regulated kinase 5 (ERK5) plays in various diseases, particularly cancer and inflammation, has grown. Phenotypes observed from genetic knockdown or deletion of ERK5 suggested that targeting ERK5 could have therapeutic potential in various disease settings, motivating the development of potent and selective ATP-competitive ERK5 inhibitors. However, these inhibitors were unable to recapitulate the effects of genetic loss of ERK5, suggesting that ERK5 may have key kinase-independent roles. To investigate potential non-catalytic functions associated with ERK5, we report here the development of INY-06-061, a potent and selective heterobifunctional degrader of ERK5. In contrast to results reported through genetic knockdown of ERK5, INY-06-061-induced ERK5 degradation did not induce anti-proliferative effects in multiple cancer cell lines or suppress inflammatory responses in primary endothelial cells. Thus, we have developed and characterized a chemical tool useful for validating phenotypes reported to be associated with genetic ERK5 ablation and for guiding future ERK5-directed drug discovery efforts.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:58:34.659.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMTpro; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-16 13:50:27	ID requested
1	2022-10-13 12:38:36	announced
⏵ 2	2023-11-14 08:58:35	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Targeted Protein Degradation, ERK5, Degrader

Eric Fischer
contact affiliation	Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
contact email	eric_fischer@dfci.harvard.edu
lab head
Eric Fischer
contact affiliation	Dana-Farber Cancer Institute
contact email	eric_fischer@dfci.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036104
     1. Label: PRIDE project
     2. Name: Acute pharmacological degradation of ERK5 does not inhibit cellular immune response or proliferation