A cyclin D-CDK6 dimer helps to reshuffle cyclin-dependent kinase inhibitors (CKI) to overcome TGF-beta-mediated arrest and maintain CDK2 activity

References

• Sherr CJ, Beach D, Shapiro GI. Targeting CDK4 and CDK6: from discovery to therapy. Cancer Discov. 2016;6(4):353–367.
   PubMed Web of Science ®Google Scholar
• Blain SW. Switching cyclin D-Cdk4 kinase activity on and off. Cell Cycle. 2008;7(7):892–898.
   PubMed Web of Science ®Google Scholar
• Guiley KZ, Stevenson JW, Lou K, et al. p27 allosterically activates cyclin-dependent kinase 4 and antagonizes palbociclib inhibition. Science. 2019;366(6471):6471.
   Web of Science ®Google Scholar
• Patel P, Asbach B, Shteyn E, et al. Brk/protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4. Mol Cell Biol. 2015;35(9):1506–1522. .
   PubMed Web of Science ®Google Scholar
• Sherr CJ. Surprising regulation of cell cycle entry. Science. 2019;366(6471):1315–1316.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Alexander PB, Xf W. TGF-β family signaling in the control of cell proliferation and survival. Cold Spring Harb Perspect Biol. 2017;9(4):a022145.
   Web of Science ®Google Scholar
• Ingham M, Schwartz GK. Cell-cycle therapeutics come of age. J Clin Oncol. 2017;35(25):2949–2959.
   PubMed Web of Science ®Google Scholar
• Guarducci C, Bonechi M, Boccalini G, et al. Mechanisms of resistance to CDK4/6 inhibitors in breast cancer and potential biomarkers of response. Breast Care (Basel). 2017;12(5):304–308. .
   PubMed Web of Science ®Google Scholar
• Ewen ME, Sluss HK, Whitehouse LL, et al. TGFß inhibition of CDK4 synthesis is linked to cell cycle arrest. Cell. 1993;74(6):1009–1020.
   PubMed Web of Science ®Google Scholar
• Warner BJ, Blain SW, Seoane J, et al. Myc downregulation by transforming growth factor beta required for activation of the p15(Ink4b) G(1) arrest pathway.. Mol Cell Biol. 1999;19(9):5913–5922.
   PubMed Web of Science ®Google Scholar
• Reynisdottir I, Polyak K, Iavarone A, et al. Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta. Genes Dev. 1995;9(15):1831–1845.
   PubMed Web of Science ®Google Scholar
• James MK, Ray A, Leznova D, et al. Differential modification of p27Kip1 controls its cyclin D-cdk4 inhibitory activity. Mol Cell Biol. 2008;28(1):498–510.
   PubMed Web of Science ®Google Scholar
• Grossel MJ, Baker GL, Hinds PW. cdk6 can shorten G(1) phase dependent upon the N-terminal INK4 interaction domain. J Biol Chem. 1999;274(42):29960–29967.
   PubMed Web of Science ®Google Scholar
• Matsushime H, Ewen ME, Strom DK, et al. Identification and properties of an atypical catalytic subunit (p34PSK-J3/cdk4) for mammalian D type G1 cyclins. Cell. 1992;71(2):323–334. .
   PubMed Web of Science ®Google Scholar
• Van Den Heuvel S, Harlow E. Distinct roles for cyclin-dependent kinases in cell cycle control. Science. 1993;262(5142):2050–2054.
   PubMed Web of Science ®Google Scholar
• Wölfel T, Hauer M, Schneider M, et al. A p16INK4A-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in human melanoma.. Science. 1995;269(5228):1281–1284. .
   PubMed Web of Science ®Google Scholar
• Parry D, Mahony D, Wills K, et al. CyclinD-cdk subunit arrangement is dependent on the availability of competing Ink4 and p21 class inhibitors. Mol Cell Biol. 1999;19:1775–1783.
   PubMed Web of Science ®Google Scholar
• Gu Y, Rosenblatt J, Morgan DO. Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 And Tyr15. Embo J. 1992;11(11):3995–4005.
   PubMed Web of Science ®Google Scholar
• Mahony D, Parrry DA, Active EL. CDK6 complexes are predominantly nuclear and represent only a minority of the CDK6 in T cells. Oncogene. 1998;16(5):603–11.
   PubMed Web of Science ®Google Scholar
• McConnell BB, Gregory FJ, Stott FJ, et al. Induced expression of p16Ink4a inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-cdk inhibitor complexes.. Mol Cell Biol. 1999;19(3):1981–1989.
   PubMed Web of Science ®Google Scholar
• Stepanova L, Leng X X, Sg P, et al. Mammalian p50cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes CDK4. Genes Dev. 1996;10(12):1491–1502.
   PubMed Web of Science ®Google Scholar
• Malumbres M. Cyclin-dependent kinases. Genome Biol. 2014;15(6):122.
   PubMed Web of Science ®Google Scholar
• Wood DJ, Endicott JA. Structural insights into the functional diversity of the CDK-cyclin family. Open Biol. 2018;8(9):180112.
   PubMed Web of Science ®Google Scholar
• Knudsen ES, Kumarasamy V, Ruiz A, et al. Cell cycle plasticity driven by MTOR signaling: integral resistance to CDK4/6 inhibition in patient-derived models of pancreatic cancer. Oncogene. 2019 May;38(18):3355–3370
   PubMed Web of Science ®Google Scholar
• Katlinskaya YV, Katlinski KV, Yu Q, et al. Suppression of type I interferon signaling overcomes oncogene-induced senescence and mediates melanoma development and progression. Cell Rep. 2016;15(1):171–180. .
   PubMed Web of Science ®Google Scholar
• Li Z, Razavi P, Li Q, et al. Loss of the FAT1 tumor suppressor promotes resistance to cdk4/6 inhibitors via the hippo pathway. Cancer Cell. 2018;34(6):893–905 e8. .
   PubMed Web of Science ®Google Scholar
• Tsutsui T, Hesabi B, Moons DS, et al. Targeted disruption of CDK4 delays cell cycle entry with enhanced p27(kip1) activity. Mol Cell Biol. 1999;19(10):7011–7019.
   PubMed Web of Science ®Google Scholar
• Álvarez-Fernández M, Malumbres M. Mechanisms of sensitivity and resistance to CDK4/6 inhibition. Cancer Cell. 2020;37(4):514–529.
   PubMed Web of Science ®Google Scholar
• Sicinski P, Donaher JL, Parker SB, et al. Cyclin D1 provides a link between development and oncogenesis in the retina and breast.. Cell. 1995;82(4):621–630. .
   PubMed Web of Science ®Google Scholar
• Yu Q, Sicinska E, Geng Y, et al. Requirement for CDK4 kinase function in breast cancer. Cancer Cell. 2006;9(1):23–32. .
   PubMed Web of Science ®Google Scholar
• Landis WM, Pawlyk SB, Li T, et al. Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis. Cancer Cell. 2006;9(1):13–22.
   PubMed Web of Science ®Google Scholar