PXD036327

PXD036327 is an original dataset announced via ProteomeXchange.

Title	Targeting MCL-1 Causes DNA Damage and Cell Cycle Arrest Independent from Apoptosis Induction
Description	MCL-1 is a high-priority target due to its dominant role in the pathogenesis and chemoresistance of cancer, yet clinical trials of MCL-1 inhibitors are revealing toxic side-effects. MCL-1 biology is complex, extending beyond apoptotic regulation and confounded by its multiple isoforms, domains of unknown structure and function, and challenges in distinguishing noncanonical activities from the apoptotic response. We find that, in the presence or absence of an intact mitochondrial apoptotic pathway, genetic deletion or pharmacologic targeting of MCL-1 triggers DNA damage and cell cycle arrest. Indeed, the cancer cell susceptibility profile of MCL-1 inhibitors better matches that of anti-proliferative than pro-apoptotic drugs, expanding their potential therapeutic applications, including synergistic combinations, but heightening therapeutic window concerns. Proteomic profiling across cell cycle stages provides a resource for mechanistic dissection and revealed MCM among other MCL-1-interacting nuclear protein complexes that link MCL-1 to the regulation of DNA integrity and cell cycle progression.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_09:11:21.071.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-26 07:29:57	ID requested
⏵ 1	2025-05-06 09:11:21	announced

10.1016/j.celrep.2023.113176;

Adhikary U, Paulo JA, Godes M, Roychoudhury S, Prew MS, Ben-Nun Y, Yu EW, Budhraja A, Opferman JT, Chowdhury D, Gygi SP, Walensky LD, Targeting MCL-1 triggers DNA damage and an anti-proliferative response independent from apoptosis induction. Cell Rep, 42(10):113176(2023) [pubmed]

submitter keyword: cell cycle arrest, cancer, therapeutic window, BCL-2 family,MCL-1, cell proliferation, apoptosis, DNA damage, chemotherapy, affinity enrichment mass spectrometry

Loren D. Walensky
contact affiliation	Department of Pediatric Oncology Linde Program in Cancer Chemical Biology Dana-Farber Cancer Institute Boston, MA 02215 USA
contact email	Loren_Walensky@dfci.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD036327

PRIDE project URI

• PRIDE
  1. PXD036327
     1. Label: PRIDE project
     2. Name: Targeting MCL-1 Causes DNA Damage and Cell Cycle Arrest Independent from Apoptosis Induction