⮝ Full datasets listing

PXD043233

PXD043233 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleFuzzy interactions between the auto-phosphorylated C-terminus and the kinase domain of CK1δ inhibits activation of TAp63α
DescriptionThe p53 family member TAp63α plays an important role in maintaining the genetic integrity in oocytes. DNA damage, in particular DNA double strand breaks, lead to the transformation of the inhibited, only dimeric conformation into the active tetrameric one that results in the initiation of an apoptotic program. Activation requires phosphorylation by the kinase CK1 which phosphorylates TAp63α at four positions. The third phosphorylation event is the decisive step that transforms TAp63α into the active state. This third phosphorylation, however, is ~20 times slower than the first two phosphorylation events. This difference in the phosphorylation kinetics constitutes a safety mechanism that allows oocytes with a low degree of DNA damage to survive. So far these kinetic investigations of the phosphorylation steps have been performed with the isolated CK1 kinase domain. However, all CK1 enzymes contain C-terminal extensions that become auto-phosphorylated and inhibit the activity of the kinase. Here we have investigated the effect of auto-phosphorylation of the C-terminus in the kinase CK1δ and show that it slows down phosphorylation of the first two sites in TAp63α but basically inhibits the phosphorylation of the third site. We have identified up to ten auto-phosphorylation sites in the CK1δ C-terminal domain and show that all of them interact with the kinase domain in a “fuzzy” way in which not a single site is particularly important. Through mutation analysis we further show that hydrophobic amino acids following the phosphorylation site are important for a substrate to be able to successfully compete with the auto-inhibitory effect of the C-terminal domain. This auto-phosphorylation adds a new layer to the regulation of apoptosis in oocytes.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:05:05.900.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChristian Münch
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-06-23 05:06:12ID requested
12023-10-06 05:27:16announced
22023-11-14 09:05:51announced2023-11-14: Updated project metadata.
32024-10-22 06:05:06announced2024-10-22: Updated project metadata.
Publication List
Lambert M, Gebel J, Trejtnar C, Wesch N, Bozkurt S, Adrian-Allgood M, L, ö, hr F, M, ü, nch C, D, ö, tsch V, . Sci Rep, 13(1):16423(2023) [pubmed]
10.1038/s41598-023-43515-x;
Keyword List
submitter keyword: CK1, ovarian reserve, p53 family, quality control, phosphorylation,p63, tetramerization, DNA damage, premature ovarian insufficiency
Contact List
Christian Münch
contact affiliationInstitute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany Frankfurt Cancer Institute, Frankfurt am Main, Germany Cardio-Pulmonary Institute, Frankfurt am Main, Germany
contact emailbozkurt@med.uni-frankfurt.de
lab head
Christian Münch
contact affiliationGoethe University Frankfurt
contact emailch.muench@em.uni-frankfurt.de
dataset submitter
Full Dataset Link List
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/2023/10/PXD043233
PRIDE project URI
Repository Record List
[ + ]