PXD030773-2

PXD030773 is an original dataset announced via ProteomeXchange.

Title	The proto-oncogene TCL1A deregulates mitotic checkpoint transition and genomic stability in CLL
Description	Upregulation of the proto-oncogene TCL1A is causally implicated in various B- and T-cell malignancies. High-level TCL1A correlates with aggressive disease features and inferior clinical outcomes. However, molecular and cell-biological consequences of TCL1A dysregulation are not fully elucidated. Here, we identify CDC20 and other molecules of the safeguarding cell cycle checkpoints as novel TCL1A-interactors. In different model systems of B-cell leukemia/lymphoma, TCL1A overexpression accelerated cell cycle transition, impaired apoptotic damage responses in association with pronounced chromosome mis-segregation and caused cellular aneuploidy. In primary CLL samples, low CDC20 expression correlated with high expression of TCL1A and more aggressive disease characteristics. In line, a low CDC20 expression was a marker for reduced progression-free survival in CLL patients. Finally, knockdown of CDC20 in TCL1A-initiated murine lymphomas promoted chromosome disbalances and leukemia outgrowth. Overall, we discovered a cell-cycle associated effect of TCL1A by interfering with a proficient cell cycle transition. This adds to our concept of TCL1A’s transforming impact by targeting genome stability.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:54:11.294.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Prerana Wagle
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-06 01:35:05	ID requested
1	2022-11-14 04:13:44	announced
⏵ 2	2023-11-14 08:54:11	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: TCL1A, leukemia, CDC20, mitotic checkpoint, aneuploidy

Marco Herling
contact affiliation	1. Department I of Internal Medicine, Center for Integrated Oncology (CIO), Aachen-Bonn- Cologne-Duesseldorf, Excellence Cluster for Cellular Stress Response and Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), University of Cologne (UoC), 50937 Cologne, Germany 2. Department of Hematology and Cellular Therapy, University of Leipzig, Leipzig, Germany
contact email	marco.herling@medizin.uni-leipzig.de
lab head
Prerana Wagle
contact affiliation	CECAD Research Center
contact email	proteomics-facility@uni-koeln.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/2022/11/PXD030773

PRIDE project URI

• PRIDE
  1. PXD030773
     1. Label: PRIDE project
     2. Name: The proto-oncogene TCL1A deregulates mitotic checkpoint transition and genomic stability in CLL