The DOI matches its Crossref record; 78 of the 81 references it cites were found in a registry or an index.
A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis
Open accessAbstract
In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185BCR-ABL+ B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16INK4a and the pro-angiogenic factor VEGF-A. This function is independent of CDK6's kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16INK4a, providing an internal safeguard. However, in the absence of p16INK4a, CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6's central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16INK4a.
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“Moreover, ATP-competitive inhibitors cannot disrupt the scaffolding functions of CDK6, which is important for the transcription function of CDK6 [124, 125].”
From Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies (2020) · cites this paper as [124]
Experimental — accuracy not yet measuredIn the citing paper
“On the other hand, CDK6-specific functions include participating as part of a transcription complex that regulates expression of p16INK4a and VEGF-A[5]”
From Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 (2019) · cites this paper as [5]
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Cites
1 retracted
Oncogenic activity of Cdc6 through repression of the INK4/ARF locus
González, S., Klatt, P., Delgado, S., Conde, E., López‐Ríos, F., Sánchez‐Céspedes, M., Méndez, J., Antequera, F., & Serrano, M. (2006) · Nature · doi:10.1038/nature04585 · Cited by 186
RetractedCDK inhibitors: positive and negative regulators of G1-phase progression
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“Although p16 is also able to promote oncogene-induced senescence (Campisi, 2012), we failed to obtain any evidence of senescence.”
BackgroundRAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement
Shinkai, Y. (1992) · Cell · doi:10.1016/0092-8674(92)90029-c · Cited by 2,711
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Role of the INK4a Locus in Tumor Suppression and Cell Mortality
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Self-citationCyclin D as a therapeutic target in cancer
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Cited by
Sorted by citations
Cell cycle proteins as promising targets in cancer therapy
Otto, T., & Siciński, P. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.138 · Cited by 1,931
Malumbres, M. (2014) · Genome biology · doi:10.1186/gb4184 · Cited by 1,730
Self-citationCDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation
Deng, J., Wang, E. S., Jenkins, R. W., Li, S., Dries, R., Yates, K., Chhabra, S., Huang, W., Liu, H., Aref, A. R., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0915 · Cited by 770
“The digested NFATc3 and His-GB1 were separated and further purified using size exclusion chromatography (GE Healthcare Life Sciences “Superdex 75 10/300 GL”).”
BackgroundInfluentialTargeting cell-cycle machinery in cancer
Suski, J. M., Braun, M., Strmiska, V., & Siciński, P. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.03.010 · Cited by 587
Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases
Hydbring, P., Malumbres, M., & Sicinski, P. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.27 · Cited by 528
Self-citation
Metadata
- Authors
- Kollmann, K., Heller, G., Schneckenleithner, C., Warsch, W., Scheicher, R., Ott, R. G., Schäfer, M., Fajmann, S., Schlederer, M., Schiefer, A.-I., Reichart, U., Mayerhofer, M., Hoeller, C., Zöchbauer-Müller, S., Kerjaschki, D., Bock, C., Kenner, L., Hoefler, G., Freissmuth, M., Green, A. R., Moriggl, R., Busslinger, M., Malumbres, M., & Sexl, V.
- Affiliations
- University of Veterinary Medicine Vienna (AT)
- Comprehensive Cancer Center Vienna (AT)
- Research Institute of Molecular Pathology (AT)
- Medical University of Vienna (AT)
- Austrian Academy of Sciences (AT)
- Ludwig Boltzmann Institute for Cancer Research (AT)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Spanish National Cancer Research Centre (ES)
- Corresponding author
- Sexl, Veronika
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 24
- Issue
- 2
- Pages
- 167-181
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC5637299
- OpenAlex
- W2152600133
- Cited by
- 313
- References
- 81
- Citations by year
- 2026: 16 · 2025: 22 · 2024: 27 · 2023: 23 · 2022: 35 · 2021: 33 · 2020: 42 · 2019: 25 · 2018: 20 · 2017: 20 · 2016: 17 · 2015: 19 · 2014: 10 · 2013: 4
- FWCI
- 8.93
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-08-08)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (079249, 100140)
- Medizinische Universität Wien
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- CDK6, CDK4, p16INK4a, VEGF-A, tumor angiogenesis, B-cell acute lymphoblastic leukemia, BCR-ABL, transcriptional regulation, cell cycle, kinase-independent function, lymphoid malignancies, cell proliferation, hematologic malignancies
- MeSH terms
- Animals, Cell Cycle, Humans, Mice, Inbred C57BL, Mice, Nude, Mice, Transgenic, Neoplasms, Neovascularization, Pathologic, Leukemia, B-Cell, Lymphoma, B-Cell, Cyclin-Dependent Kinase 6, Mice
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