Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2Dgene.[1][2]
The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown to form a stable complex with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. The abundance of the transcript of this gene was found to oscillate in a cell-cycle dependent manner with the lowest expression at mid G1 and a maximal expression during S phase. The negative regulation of the cell cycle involved in this protein was shown to participate in repressing neuronal proliferation, as well as spermatogenesis. Two alternatively spliced variants of this gene, which encode an identical protein, have been reported.[2]
Note, this protein should not be confused with p19-ARF (mouse) or the human equivalent p14ARF, which are alternative products of the CDKN2A gene.
References
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Schwaller J, Pabst T, Koeffler HP, et al. (1997). "Expression and regulation of G1 cell-cycle inhibitors (p16INK4A, p15INK4B, p18INK4C, p19INK4D) in human acute myeloid leukemia and normal myeloid cells". Leukemia. 11 (1): 54–63. doi:10.1038/sj.leu.2400522. PMID9001419.
Russo AA, Tong L, Lee JO, et al. (1998). "Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a". Nature. 395 (6699): 237–43. doi:10.1038/26155. PMID9751050.
Brotherton DH, Dhanaraj V, Wick S, et al. (1998). "Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d". Nature. 395 (6699): 244–50. doi:10.1038/26164. PMID9751051.
Baumgartner R, Fernandez-Catalan C, Winoto A, et al. (1998). "Structure of human cyclin-dependent kinase inhibitor p19INK4d: comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16INK4a". Structure. 6 (10): 1279–90. doi:10.1016/S0969-2126(98)00128-2. PMID9782052.
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Bartkova J, Thullberg M, Rajpert-De Meyts E, et al. (2000). "Lack of p19INK4d in human testicular germ-cell tumours contrasts with high expression during normal spermatogenesis". Oncogene. 19 (36): 4146–50. doi:10.1038/sj.onc.1203769. PMID10962575.
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Arcellana-Panlilio MY, Egeler RM, Ujack E, et al. (2002). "Evidence of a role for the INK4 family of cyclin-dependent kinase inhibitors in ovarian granulosa cell tumors". Genes Chromosomes Cancer. 35 (2): 176–81. doi:10.1002/gcc.10108. PMID12203782.
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