Disease relevance of Cdk2ap1

• Human oral cancers in vivo did not exhibit immunostaining for DOC-1 [1].

High impact information on Cdk2ap1

• Deleted in oral cancer-1 (doc-1), a novel oral tumor suppressor gene [2].
• Transfection of the full-length doc-1 cDNA into malignant hamster oral keratinocytes alters the behavior of the recipients in terms of morphology, growth rate, and anchorage-independent growth, suggesting reversion of transformation phenotypes [2].
• We propose that doc-1 is a novel tumor suppressor gene in oral cancer development [2].
• The full-length doc-1 cDNA encodes an 87 amino acid product that shows a significant homology to one of the seven novel genes induced in mouse fibroblasts by TNF-alpha [2].
• Doc-1 is an evolutionarily conserved gene exhibiting loss of heterozygosity and marked reduction in expression in malignant hamster oral keratinocytes [2].

Biological context of Cdk2ap1

• Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene Doc-1 [1].
• We identified four exons in the entire human doc-1 gene and determined the intron-exon boundaries [1].
• Using a human doc-1 cosmid as a probe, human doc-1 is mapped to chromosome 12q24 [1].
• Thus, the progression of chondrogenic differentiation requires down-regulation of CDK2-associated kinase with an increase in p21 protein and subsequent degradation of this protein by a proteasomal pathway [3].

Anatomical context of Cdk2ap1

• In oral keratinocytes, expression of DOC-1 is restricted to normal oral keratinocytes [1].
• By immunostaining of normal human mucosa, DOC-1 is detected in both the cytoplasm and nuclei of basal oral keratinocytes; while in suprabasilar cells, it is primarily found in the nuclei [1].
• Cdk2-associated kinase activity was strongly induced in mitogen-treated B cells [4].
• DOC-1 mRNA was detected all tissues examined, but only in the uterus and cervix was markedly increased 12 hr after E administration, it returned to basal level by 48 hr [5].

Regulatory relationships of Cdk2ap1

• However, whereas CDK2-associated kinase activity was completely inhibited by TGF beta in the wild-type cells, it was reduced only slightly in the RB mutant cells [6].

Other interactions of Cdk2ap1

• Furthermore, this cdk2-associated kinase activity is required for G(0)-G(1) traverse in some role other than the regulation of E2F-dependent transcription [7].
• In unsynchronized B-lymphoma cells, anti-mu cross-linking of membrane immunoglobulin M leads to an accumulation of the hypophosphorylated form of pRB, a decrease in the abundance of one form of cyclin A, and inhibition of cyclin A and cdk2-associated kinase activity [8].

Analytical, diagnostic and therapeutic context of Cdk2ap1

• Sequence analysis showed 98% identity between human and hamster doc-1 protein sequences [1].
• Here, we report the molecular cloning and the functional characterization of the human ortholog of the hamster doc-1 gene [1].

References