Disease relevance of CKAP4

• Thus, the differential regulation of hTERT and VEGF in p63-positive breast carcinomas may contribute to the clinically more aggressive behavior of these neoplasms [1].
• The expression of TIMP1 suggests that the anti-proteolytic stimuli may be preponderant in p63-positive carcinomas. hTERT activity is associated with nodal metastases and cellular proliferation [1].
• Upon digestion with Bacillus cereus phospholipase C, amphiphilic p63 is shown to lose its myristic acid label and to acquire concomitantly the characteristic electrophoretic mobility and solubility behavior of hydrophilic p63 [2].
• Homeobox gene Dlx3 is regulated by p63 during ectoderm development: relevance in the pathogenesis of ectodermal dysplasias [3].
• CKAP4/p63 Is a Receptor for the Frizzled-8 Protein-related Antiproliferative Factor from Interstitial Cystitis Patients [4].

High impact information on CKAP4

• Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells [5].
• There is a significant, but complex, relationship between p63 target sites and p63-responsive genes, with DeltaNp63 isoforms being linked to transcriptional activation [5].
• Using tiled microarrays covering the entire human genome, we identify approximately 5800 target sites for p63, a p53 homolog essential for stratified epithelial development. p63 targets are enriched for genes involved in cell adhesion, proliferation, death, and signaling pathways [5].
• The quality of the derived DNA sequence motif for p63 targets correlates with binding strength binding in vivo, but only a small minority of motifs in the genome is bound by p63 [5].
• The tyrosine phosphorylation of p63 can be induced independently of other substrates when using a single CD2 mAb recognizing the D66 epitope of the molecule [6].

Chemical compound and disease context of CKAP4

• Antibodies raised against the p63 carboxy-terminal peptide inhibited poliovirus replicase and polyuridylic acid polymerase activities in vitro, providing strong support for earlier suggestions that these activities are a property of a single virus-specific polypeptide [7].
• Formalin-fixed paraffin-embedded tissue sections of small cell carcinomas and poorly differentiated squamous cell carcinomas underwent immunohistochemical staining with antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A) [8].
• Gleevec suppresses p63 expression in head and neck squamous cell carcinoma despite p63 activation by DNA-damaging agents [9].

Biological context of CKAP4

• This study aims to verify the relationship between p63 expression and several clinicopathological features and tumor markers of clinical significance in breast pathology including key regulators of the cell cycle, oncogenes, apoptosis-related proteins, metalloproteinases and their inhibitors [1].
• Mitotic phosphorylation can be prevented by mutation of serines 3, 17, and 19 in the cytoplasmic domain of CLIMP-63 [10].
• Metabolic labeling with (32)P showed that CLIMP-63 is a phosphoprotein with increased phosphorylation during mitosis [10].
• Overexpression of the phospho-mimicking mitotic form of CLIMP-63 in interphase cells leads to a collapse of the ER around the nucleus, leaving the microtubular network intact [10].
• An additional remarkable feature of p63 is that it becomes reversibly palmitoylated when intracellular protein transport is blocked by the drug brefeldin A [11].

Anatomical context of CKAP4

• Immunofluorescence microscopy demonstrated that p63 was located principally in the endoplasmic reticulum but was also detected in significant quantities on the surface of human VSMC [12].
• p63, a p53 homologue, is a myoepithelial cell marker in the normal mammary gland but p63-positive neoplastic cells may be found in up to 11% of invasive breast carcinomas [1].
• Concentration of CLIMP-63 into patches may enhance microtubule binding on the cytosolic side and contribute to ER morphology by the formation of a protein scaffold in the lumen of the ER [13].
• The findings indicate that the luminal segment of CLIMP-63 is necessary and sufficient for oligomerization into alpha-helical complexes that prevent nuclear envelope localization [13].
• Here we first characterize young primary NHP cells as CK5(+)/CK18(+) intermediate basal cells that also express several other putative stem/progenitor cell markers including p63, CD44, alpha2beta1, and hTERT [14].

Associations of CKAP4 with chemical compounds

• When these residues are mutated to glutamic acid, and hence mimic mitotic phosphorylation, CLIMP-63 does no longer bind to microtubules in vitro [10].
• This ultimately suggests that p63 may represent in fact the 62-kD protein that associates with GAP after tyrosine phosphorylation [6].
• Apoptosis induced by loss of p63 was rescued by signalling downstream of beta4 integrin [15].
• Mutational analysis of the 106-amino acid cytoplasmic tail of p63 revealed that the NH2-terminal 23 amino acids are necessary for retention [16].
• When p63 was solubilized with Triton X-100 and subjected to centrifugation at 100,000 g, it formed large, insoluble oligomers, particularly at neutral pH and below [16].

Other interactions of CKAP4

• The recently identified 63 kDa membrane protein, p63, is a resident protein of a membrane network interposed in between rough ER and Golgi apparatus [11].

Analytical, diagnostic and therapeutic context of CKAP4

• In confirmation of this, a monoclonal antibody raised against authentic human p63 recognized the isolated protein in Western blotting [12].
• Histological examination revealed the presence of mucin-producing cells, and immunohistochemistry using antibodies against p63 and keratin 14 showed the presence of basal cells [17].
• Deleting the luminal but not cytosolic segment of CLIMP-63 abrogated subdomain-specific localization, as visualized by confocal microscopy in living cells and by immunoelectron microscopy using ultrathin cryosections [13].
• The recombinant full-length luminal segment of CLIMP-63 formed alpha-helical 91-nm long rod-like structures as evident by circular dichroism spectroscopy and electron microscopy [13].
• A reversibly palmitoylated resident protein (p63) of an ER-Golgi intermediate compartment is related to a circulatory shock resuscitation protein [11].

References