CDKN2D
Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene.[5][6]
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
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000129355 – Ensembl, May 2017
- ^ a b c 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, Sherr CJ, Downing JR (Mar 1996). "Molecular cloning, expression pattern, and chromosomal localization of human CDKN2D/INK4d, an inhibitor of cyclin D-dependent kinases". Genomics. 29 (3): 623–30. doi:10.1006/geno.1995.9957. PMID 8575754.
- ^ a b "Entrez Gene: CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)".
- ^ Dehkordi, Shiva Kazempour; Walker, Jamie; Sah, Eric; Bennett, Emma; Atrian, Farzaneh; Frost, Bess; Woost, Benjamin; Bennett, Rachel E.; Orr, Timothy C.; Zhou, Yingyue; Andhey, Prabhakar S.; Colonna, Marco; Sudmant, Peter H.; Xu, Peng; Wang, Minghui; Zhang, Bin; Zare, Habil; Orr, Miranda E. (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
[edit]- Hirai H, Roussel MF, Kato JY, et al. (1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. Biol. 15 (5): 2672–81. doi:10.1128/MCB.15.5.2672. PMC 230497. PMID 7739547.
- Chan FK, Zhang J, Cheng L, et al. (1995). "Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4". Mol. Cell. Biol. 15 (5): 2682–8. doi:10.1128/MCB.15.5.2682. PMC 230498. PMID 7739548.
- Guan KL, Jenkins CW, Li Y, et al. (1996). "Isolation and characterization of p19INK4d, a p16-related inhibitor specific to CDK6 and CDK4". Mol. Biol. Cell. 7 (1): 57–70. doi:10.1091/mbc.7.1.57. PMC 278612. PMID 8741839.
- 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. PMID 9001419.
- 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. Bibcode:1998Natur.395..237R. doi:10.1038/26155. PMID 9751050. S2CID 204997058.
- 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. Bibcode:1998Natur.395..244B. doi:10.1038/26164. PMID 9751051. S2CID 13337394.
- 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. 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): 1663–76. doi:10.1038/sj.onc.1202466. PMID 10208428.
- Newton Bishop JA, Harland M, Bennett DC, et al. (1999). "Mutation testing in melanoma families: INK4A, CDK4 and INK4D". Br. J. Cancer. 80 (1–2): 295–300. doi:10.1038/sj.bjc.6690354. PMC 2363010. PMID 10390011.
- Zindy F, Cunningham JJ, Sherr CJ, et al. (1999). "Postnatal neuronal proliferation in mice lacking Ink4d and Kip1 inhibitors of cyclin-dependent kinases". Proc. Natl. Acad. Sci. U.S.A. 96 (23): 13462–7. Bibcode:1999PNAS...9613462Z. doi:10.1073/pnas.96.23.13462. PMC 23970. PMID 10557343.
- Thullberg M, Bartkova J, Khan S, et al. (2000). "Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors". FEBS Lett. 470 (2): 161–6. doi:10.1016/S0014-5793(00)01307-7. PMID 10734227. S2CID 45439595.
- 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. PMID 10962575.
- Fink JR, LeBien TW (2001). "Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors". Exp. Hematol. 29 (4): 490–8. doi:10.1016/S0301-472X(01)00619-1. PMID 11301189.
- Zeeb M, Rösner H, Zeslawski W, et al. (2002). "Protein folding and stability of human CDK inhibitor p19(INK4d)". J. Mol. Biol. 315 (3): 447–57. doi:10.1006/jmbi.2001.5242. PMID 11786024.
- Matsuzaki Y, Miyazawa K, Yokota T, et al. (2002). "Molecular cloning and characterization of the human p19(INK4d) gene promoter". FEBS Lett. 517 (1–3): 272–6. doi:10.1016/S0014-5793(02)02647-9. PMID 12062451. S2CID 82054693.
- 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. PMID 12203782. S2CID 27477191.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Gevaert K, Goethals M, Martens L, et al. (2004). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nat. Biotechnol. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801. S2CID 23783563.
- Komata T, Kanzawa T, Takeuchi H, et al. (2004). "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on malignant glioma cells". Br. J. Cancer. 88 (8): 1277–80. doi:10.1038/sj.bjc.6600862. PMC 2747579. PMID 12698196.
External links
[edit]- 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.
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