PXD038102 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2023-03-11 |
AnnouncementXML | Submission_2023-03-10_19:15:55.700.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | RanadipMandal |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: Caspase-8, TMT,Cervical cancer, LC-MS/MS |
Contact List
KlausStrebhardt |
contact affiliation | Department of Gynecology School of Medicine Goethe University Frankfurt Germany |
contact email | strebhardt@em.uni-frankfurt.de |
lab head | |
RanadipMandal |
contact affiliation | J. W. Goethe University |
contact email | ranadip.mandal@kgu.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD038102
- Label: PRIDE project
- Name: The non-apoptotic function of Caspase-8 in negatively regulating the CDK9 mediated Ser2 phosphorylation of RNA Polymerase II in cervical cancer