PXD038102

PXD038102 is an original dataset announced via ProteomeXchange.

Title	The non-apoptotic function of Caspase-8 in negatively regulating the CDK9 mediated Ser2 phosphorylation of RNA Polymerase II in cervical cancer
Description	Cervical cancer is the fourth most frequently diagnosed and fatal gynecological cancer. 15-61% of all cases metastasize and develop chemoresistance, reducing the 5-year survival of cervical cancer patients to as low as 17%. Therefore, unraveling the mechanisms contributing to metastasis is critical in developing better-targeted therapies against it. Here, we have identified a novel mechanism where nuclear Caspase-8 directly interacts with and inhibits the activity of CDK9, thereby modulating RNAPII-mediated global transcription, including those of cell-migration and -invasion-associated genes. Crucially, low Caspase-8 expression in cervical cancer patients leads to poor prognosis, higher CDK9 phosphorylation at Thr186, and increased RNAPII activity in cervical cancer cell lines and patient biopsies. Caspase-NT8 knock-out cells were also more resistant to the small-molecule CDK9 inhibitor BAY1251152 in both 2D- and 3D-culture conditions. Combining BAY1251152 with Cisplatin synergistically overcame chemoresistance of Caspase-8 deficient cervical cancer cells. Therefore, Caspase-8 expression could be a marker in chemoresistant cervical tumors, suggesting CDK9 inhibitor treatment for their sensitization to Cisplatin-based chemotherapy.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:27:52.697.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ranadip Mandal
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-11 09:02:03	ID requested
1	2023-03-10 19:16:00	announced
⏵ 2	2023-11-14 08:27:53	announced	2023-11-14: Updated project metadata.

Mandal R, Raab M, R, ö, del F, Kr, ä, mer A, Kostova I, Pe, ñ, a-Llopis S, H, ä, upl B, Oellerich T, Gasimli K, Sanhaji M, Becker S, Strebhardt K, The non-apoptotic function of Caspase-8 in negatively regulating the CDK9-mediated Ser2 phosphorylation of RNA polymerase II in cervical cancer. Cell Mol Life Sci, 79(12):597(2022) [pubmed]

submitter keyword: Caspase-8, TMT,Cervical cancer, LC-MS/MS

Klaus Strebhardt
contact affiliation	Department of Gynecology School of Medicine Goethe University Frankfurt Germany
contact email	strebhardt@em.uni-frankfurt.de
lab head
Ranadip Mandal
contact affiliation	J. W. Goethe University
contact email	ranadip.mandal@kgu.de
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/2023/03/PXD038102

PRIDE project URI

• PRIDE
  1. PXD038102
     1. Label: PRIDE project
     2. Name: The non-apoptotic function of Caspase-8 in negatively regulating the CDK9 mediated Ser2 phosphorylation of RNA Polymerase II in cervical cancer