Disease relevance of Cdkn2d

• In the present study, we investigated the role of p19INK4d in the response driven by neuroblastoma cells against DNA injury caused by UV irradiation [1].
• Our data show that the p19INK4d protein is abundant in spermatocytes of normal human adult testes, whereas virtually no p19INK4d is detectable in testicular cancer, including the preinvasive carcinoma in situ stage [2].
• Mice deficient for p19, p40 or IL-12Rbeta1 are resistant to experimental autoimmune encephalomyelitis or collagen-induced arthritis [3].
• A 19-kilodalton recombinant protein (p19), which was recognized by PAb to p65 but not by MAb to p65, was detected in recombinant phage lysates [4].

High impact information on Cdkn2d

• Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d [5].
• Our data indicate that mAsh1 negatively regulates the cell cycle (e.g., via enhanced Cdkn2d, Bub1 expression), promotes differentiation (e.g., through effects on cAMP), and enhances survival by inhibiting apoptosis [6].
• INK4c and INK4d are expressed during mouse embryogenesis in stereotypic tissue-specific patterns and are also detected, together with INK4b, in tissues of young mice [7].
• In both cases, the inhibitory effect was independent of AAV DNA replication but required the AAV p5 and p19 genes, which encode proteins required for AAV DNA replication and regulation of AAV gene expression [8].
• IMCE beta-cat cells had significantly lower p19 and p53 protein levels compared to IMCE neo cells, suggesting that alterations in these two key genes may mediate the effects of beta-cat on both cellular senescence and apoptosis [9].

Biological context of Cdkn2d

• Downregulation of p19INK4d in the dentate gyrus after kainic acid-induced seizures indicated that its expression could also be modified in nondividing cells by excitotoxic stress [10].
• We have reported that histone deacetylase (HDAC) inhibitors activate a member of the INK4 family, the p19INK4d gene, causing G1 phase arrest [11].
• Northern blot and immunofluorescence analyses revealed that primary neural cells treated with SIN-1 had increased levels of p19 alternate reading frame (p19(ARF)) mRNA and protein, which is induced by MAPK and stabilizes the p53 protein [12].
• Lack of p19INK4d in human testicular germ-cell tumours contrasts with high expression during normal spermatogenesis [2].
• Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells [1].

Anatomical context of Cdkn2d

• In situ hybridization of mouse embryo sections demonstrated expression of mRNAs encoding two polypeptide inhibitors (p18INK4c and p19INK4d) of cyclin D-dependent kinase (CDK) 4 and CDK6 in the central nervous system [10].
• One hybridoma culture produced antibodies that were directed against the p19 portion of the gag precursor [13].
• The antibodies precipitated Pr76gag and the processed virion-associated p19, as well as the 75,000-molecular-weight gag fusion protein from avian erythroblastosis virus-transformed bone marrow cells [13].
• Viable or lysed mycobacteria, as well as purified cell wall lipoprotein p19, TLR2 agonist, induced RAW264.7 cells to extend actin-rich pseudopods, which impart radial spreading within 3 h, leading later to persistent cell polarization [14].
• By using a system for stable, as well as tetracycline-inducible expression of interfering RNAs (RNAi), we studied the functions of PS1 during neuronal differentiation in the murine pluripotent p19 embryonic carcinoma cell line [15].

Associations of Cdkn2d with chemical compounds

• Trichostatin A activates p18INK4c gene: differential activation and cooperation with p19INK4d gene [11].

Other interactions of Cdkn2d

• The p19INK4d and p18INK4c proteins formed complexes with either CDK4 or CDK6 in a temporal pattern consistent with the results of in situ hybridization [10].
• Therefore, p19INK4d may contribute to maintaining the quiescent state, acting as a buffer to prevent reactivation of cyclin D-dependent kinases in terminally differentiated cells [10].
• Furthermore, CarC cells have inactivated p16INK4a and p19INK4a/ARF transcription, while CarC-R and CarC-RT clones expressed p19 mRNA and protein but not p16 [16].

Analytical, diagnostic and therapeutic context of Cdkn2d

• Using gene-targeted mice lacking only IL-12 (p35-/-) or IL-23 (p19-/-), we show that the specific absence of IL-23 is protective, whereas loss of IL-12 exacerbates collagen-induced arthritis [17].
• Here we report the complete cDNA sequence encoding p19, its expression patterns in horse tissues and a Southern blot analysis of the gene in horse DNA [18].
• We have identified by 2-D Western blotting 2 phosphorylated forms of p19, a highly conserved 18-19 kDa cytosolic protein that is frequently upregulated in transformed cells and undergoes phosphorylation in mammalian cells upon activation of several signal transduction pathways [19].
• Differentiation of mouse p19 embryonic carcinoma stem cells injected into an empty zebrafish egg chorion in a microfluidic device [20].

References