phaidra.vetmeduni.ac.at o:3896 DOI 10.1016/j.isci.2024.111697 Cdk6’s functions are critically regulated by its unique C-terminus 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. eng Cyclin-Dependent Kinase Cell-Cycle Structural Basis Crystal-Structure Intrinsic Disorder Protein-Structure Inhibitor Prediction Complex Links 2025-03-06T10:03:40.581Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Schirripa;Alessia; FN:Alessia Schirripa X-ORCID:https://orcid.org/0000-0001-5446-9136 END:VCARD BEGIN:VCARD VERSION:3.0 N:Schöppe;Helge; FN:Helge Schöppe END:VCARD BEGIN:VCARD VERSION:3.0 N:Nebenfuehr;Sofie; FN:Sofie Nebenfuehr END:VCARD BEGIN:VCARD VERSION:3.0 N:Zojer;Markus; FN:Markus Zojer END:VCARD BEGIN:VCARD VERSION:3.0 N:Klampfl;Thorsten; FN:Thorsten Klampfl X-ORCID:https://orcid.org/0000-0002-6666-9773 END:VCARD BEGIN:VCARD VERSION:3.0 N:Kugler;Valentina; FN:Valentina Kugler END:VCARD BEGIN:VCARD VERSION:3.0 N:Maw;Belinda S.; FN:Belinda S. Maw X-ORCID:https://orcid.org/0000-0002-1881-0883 END:VCARD BEGIN:VCARD VERSION:3.0 N:Ceylan;Huriye; FN:Huriye Ceylan END:VCARD BEGIN:VCARD VERSION:3.0 N:Uras;Iris Z.; FN:Iris Z. Uras END:VCARD BEGIN:VCARD VERSION:3.0 N:Scheiblecker;Lisa; FN:Lisa Scheiblecker END:VCARD BEGIN:VCARD VERSION:3.0 N:Gamper;Elisabeth; FN:Elisabeth Gamper END:VCARD BEGIN:VCARD VERSION:3.0 N:Stelzl;Ulrich; FN:Ulrich Stelzl END:VCARD BEGIN:VCARD VERSION:3.0 N:Stefan;Eduard; FN:Eduard Stefan END:VCARD BEGIN:VCARD VERSION:3.0 N:Kaserer;Teresa; FN:Teresa Kaserer END:VCARD BEGIN:VCARD VERSION:3.0 N:Sexl;Veronika; FN:Veronika Sexl X-ORCID:https://orcid.org/0000-0001-9363-0412 END:VCARD BEGIN:VCARD VERSION:3.0 N:Kollmann;Karoline; FN:Karoline Kollmann X-ORCID:https://orcid.org/0000-0002-7937-4245 END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 6360680 https://phaidra.vetmeduni.ac.at/o:3896 https://phaidra.vetmeduni.ac.at/api/object/o:3896/thumbnail LOMv1.0 discipline