Splice Variants and Phosphorylated Isoforms of Cyclin D1 in Tumorigenesis

  • J. Alan DiehlEmail author
  • Karen E. Knudsen
Part of the Current Cancer Research book series (CUCR)


Mammalian cells encode three highly homologous D-type cyclins (D1, D2, D3) that associate in a tissue-specific manner with either CDK4 or CDK6 to form an active protein kinase. The D-type cyclin/CDK kinase coordinates G1 progression in response to growth factor signaling. The cyclin D/CDK4 or CDK6 kinase is the first cyclin/CDK complex to be activated in mammalian cells during G1/S transition. While the three D-type cyclins are almost indistinguishable biochemically, cyclin D1 is the most frequently overexpressed or dysregulated in human cancer. The nature of this selectivity remains to be fully understood. While overexpression of cyclin D1 and its ensuing accumulation in tumor cell nuclei frequently result from chromosomal translocations or gene amplification events, such events do not represent the sole source of cyclin D1 dysregulation in human cancer. In this chapter, we discuss the role of posttranscriptional regulation of cyclin D1, the contribution of dysregulation of such regulatory events to human cancer, and the potential therapeutic opportunities this knowledge may afford.


Cyclin D1 Cyclin D1b GSK3β Phosphorylation Alternative splicing CDK4 


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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology, Hollings Cancer CenterMedical University of South CarolinaCharlestonUSA
  2. 2.Departments of Cancer Biology, Urology, Radiation Oncology, and Medical Oncology, Sidney Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaUSA

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