Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene.56
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. The expression of this gene and its protein product (p19) is observed in neurons with neurofibrillary tangles (NFTs) and it is suggested as a marker for senescent neurons.7 Two alternatively spliced variants of this gene, which encode an identical protein, have been reported.6
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
References
- GRCh38: Ensembl release 89: ENSG00000129355 – Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000096472 – Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- Okuda T, Hirai H, Valentine VA, Shurtleff SA, Kidd VJ, Lahti JM, et al. (Mar 1996). "Molecular cloning, expression pattern, and chromosomal localization of human CDKN2D/INK4d, an inhibitor of cyclin D-dependent kinases". Genomics. 29 (3): 623–630. doi:10.1006/geno.1995.9957. PMID 8575754.
- "Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)".
- Dehkordi SK, Walker J, Sah E, Bennett E, Atrian F, Frost B, et al. (December 2021). "Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology". Nature Aging. 1 (12): 1107–1116. doi:10.1038/s43587-021-00142-3. PMC 9075501. PMID 35531351. S2CID 245059153.
Further reading
Further reading
- Hirai H, Roussel MF, Kato JY, Ashmun RA, Sherr CJ (May 1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Molecular and Cellular Biology. 15 (5): 2672–2681. doi:10.1128/MCB.15.5.2672. PMC 230497. PMID 7739547.
- Chan FK, Zhang J, Cheng L, Shapiro DN, Winoto A (May 1995). "Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4". Molecular and Cellular Biology. 15 (5): 2682–2688. doi:10.1128/MCB.15.5.2682. PMC 230498. PMID 7739548.
- Guan KL, Jenkins CW, Li Y, O'Keefe CL, Noh S, Wu X, et al. (January 1996). "Isolation and characterization of p19INK4d, a p16-related inhibitor specific to CDK6 and CDK4". Molecular Biology of the Cell. 7 (1): 57–70. doi:10.1091/mbc.7.1.57. PMC 278612. PMID 8741839.
- Schwaller J, Pabst T, Koeffler HP, Niklaus G, Loetscher P, Fey MF, et al. (January 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. PMID 9001419.
- Russo AA, Tong L, Lee JO, Jeffrey PD, Pavletich NP (September 1998). "Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a". Nature. 395 (6699): 237–243. Bibcode:1998Natur.395..237R. doi:10.1038/26155. PMID 9751050. S2CID 204997058.
- Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, et al. (September 1998). "Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d". Nature. 395 (6699): 244–250. Bibcode:1998Natur.395..244B. doi:10.1038/26164. PMID 9751051. S2CID 13337394.
- Baumgartner R, Fernandez-Catalan C, Winoto A, Huber R, Engh RA, Holak TA (October 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): 1279–1290. doi:10.1016/S0969-2126(98)00128-2. PMID 9782052.
- Schreiber M, Muller WJ, Singh G, Graham FL (1999). "Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity". Oncogene. 18 (9): 1663–1676. doi:10.1038/sj.onc.1202466. PMID 10208428.
- Newton Bishop JA, Harland M, Bennett DC, Bataille V, Goldstein AM, Tucker MA, et al. (April 1999). "Mutation testing in melanoma families: INK4A, CDK4 and INK4D". British Journal of Cancer. 80 (1–2): 295–300. doi:10.1038/sj.bjc.6690354. PMC 2363010. PMID 10390011.
- Zindy F, Cunningham JJ, Sherr CJ, Jogal S, Smeyne RJ, Roussel MF (November 1999). "Postnatal neuronal proliferation in mice lacking Ink4d and Kip1 inhibitors of cyclin-dependent kinases". Proceedings of the National Academy of Sciences of the United States of America. 96 (23): 13462–13467. Bibcode:1999PNAS...9613462Z. doi:10.1073/pnas.96.23.13462. PMC 23970. PMID 10557343.
- Thullberg M, Bartkova J, Khan S, Hansen K, Rönnstrand L, Lukas J, et al. (March 2000). "Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors". FEBS Letters. 470 (2): 161–166. Bibcode:2000FEBSL.470..161T. doi:10.1016/S0014-5793(00)01307-7. PMID 10734227. S2CID 45439595.
- Bartkova J, Thullberg M, Rajpert-De Meyts E, Skakkebaek NE, Bartek J (August 2000). "Lack of p19INK4d in human testicular germ-cell tumours contrasts with high expression during normal spermatogenesis". Oncogene. 19 (36): 4146–4150. doi:10.1038/sj.onc.1203769. PMID 10962575.
- Fink JR, LeBien TW (2001). "Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors". Experimental Hematology. 29 (4): 490–498. doi:10.1016/S0301-472X(01)00619-1. PMID 11301189.
- Zeeb M, Rösner H, Zeslawski W, Canet D, Holak TA, Balbach J (January 2002). "Protein folding and stability of human CDK inhibitor p19(INK4d)". Journal of Molecular Biology. 315 (3): 447–457. doi:10.1006/jmbi.2001.5242. PMID 11786024.
- Matsuzaki Y, Miyazawa K, Yokota T, Hitomi T, Yamagishi H, Sakai T (April 2002). "Molecular cloning and characterization of the human p19(INK4d) gene promoter". FEBS Letters. 517 (1–3): 272–276. Bibcode:2002FEBSL.517..272M. doi:10.1016/S0014-5793(02)02647-9. PMID 12062451. S2CID 82054693.
- Arcellana-Panlilio MY, Egeler RM, Ujack E, Magliocco A, Stuart GC, Robbins SM, et al. (October 2002). "Evidence of a role for the INK4 family of cyclin-dependent kinase inhibitors in ovarian granulosa cell tumors". Genes, Chromosomes & Cancer. 35 (2): 176–181. doi:10.1002/gcc.10108. PMID 12203782. S2CID 27477191.
- Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, et al. (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–569. doi:10.1038/nbt810. PMID 12665801. S2CID 23783563.
- Komata T, Kanzawa T, Takeuchi H, Germano IM, Schreiber M, Kondo Y, et al. (April 2003). "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on malignant glioma cells". British Journal of Cancer. 88 (8): 1277–1280. doi:10.1038/sj.bjc.6600862. PMC 2747579. PMID 12698196.
External links
External links
- CDKN2D human gene location in the UCSC Genome Browser.
- CDKN2D human gene details in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P55273 (Cyclin-dependent kinase 4 inhibitor D) at the PDBe-KB.



