Title (eng)
Cdk6’s functions are critically regulated by its unique C-terminus
Helge Schöppe
Valentina Kugler
Ulrich Stelzl
Eduard Stefan
Teresa Kaserer
Abstract (eng)
The vital cell cycle machinery is tightly regulated and alterations of its central signaling hubs are a hallmark of cancer. The activity of CDK6 is controlled by interaction with several partners including cyclins and INK4 proteins, which have been shown to mainly bind to the amino-terminal lobe. We analyzed the impact of CDK6's C-terminus on its functions in a leukemia model, revealing a central role in promoting proliferation. C-terminally truncated Cdk6 (Cdk6 D C) shows reduced nuclear translocation and therefore chromatin interaction and fails to enhance proliferation and disease progression. The combination of proteomic analysis and protein modeling highlights that Cdk6's C-terminus is essential for protein flexibility and for its binding potential to cyclin D, p27 Kip1 and INK4 proteins but not cyclin B. We demonstrate that the C-terminus is a unique and essential part of the CDK6 protein, regulating interaction partner binding and therefore CDK6's functionality.
Keywords (eng)
Cyclin-Dependent KinaseCell-CycleStructural BasisCrystal-StructureIntrinsic DisorderProtein-StructureInhibitorPredictionComplexLinks
Type (eng)
Language
[eng]
Persistent identifier
Is in series
Title (eng)
iScience
Volume
28
ISSN
2589-0042
Issued
2025
Number of pages
22
Publication
MDPI
Version type (eng)
Date issued
2025
Access rights (eng)
License
Rights statement (eng)
© 2025 The Authors
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DOI
https://phaidra.vetmeduni.ac.at/o:3896
https://doi.org/10.1016/j.isci.2024.111697 - Content
- DetailsObject typePDFDocumentFormatapplication/pdfCreated06.03.2025 10:03:39 UTC
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