Cyclin-dependent kinase 4 inhibitor D is an
enzyme that in humans is encoded by the CDKN2Dgene.[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.
^"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.
PMID8575754.
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.
PMID11786024.
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.
S2CID27477191.
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.
PMID12665801.
S2CID23783563.