Disease relevance of PCBD1

• The Mirk-binding protein DCoH has been shown to be selectively expressed in colon carcinomas but not in normal tissue [1].
• Whereas only 4 of 25 benign nevi reacted with DCoH/PCD-specific antibodies, high protein levels were detectable in melanoma cell lines and 13 of 15 primary malignant melanoma lesions [2].
• In addition to human colon cancer, this is the second report about the overexpression of DCoH/PCD in human tumor cells indicating that the protein might be involved in cancerogenesis [2].
• We investigated colorectal tumors and colorectal tumor cell lines as compared to normal colon samples in search of a potential differential expression of PCD/DCoH [3].
• Dimer stabilization in hepatoma cells is mediated by a heat-labile association with an 11kD polypeptide, analogous to the DCoH cofactor identified in rat liver by Mendel et al [4].

Psychiatry related information on PCBD1

• Factor analysis of the MOS-HIV identified two factors (Mental Health Summary scores and Physical Health Summary scores, or MHS and PHS), accounting for 63% total variance [5].
• The purpose of this study was to determine the ability of this VF confirmation algorithm to recognize nonsustained VT, and to analyze the reasons for failure of the PCD device to abort shock therapy for nonsustained VT despite use of this VF confirmation algorithm [6].
• Data from this assessment was employed to facilitate an evidence-based approach to decision-making regarding conversion to electronic documentation at local and PHS levels [7].
• CONCLUSIONS: PCD is a chronic condition which has a progressively greater impact on health in the second half of life, producing significant morbidity and restriction of life style [8].

High impact information on PCBD1

• A dimerization cofactor of HNF-1 alpha (DCoH) was identified that displayed a restricted tissue distribution and did not bind to DNA, but, rather, selectively stabilized HNF-1 alpha dimers [9].
• However, DCoH did not confer transcriptional activation to the GAL4 DNA binding domain [9].
• Regulation of the HNF-1 homeodomain proteins by DCoH [10].
• The first identified example of such an accessory protein is DCoH, which confers transcriptional activity to the hepatocyte nuclear factor 1 and provides a model of how other accessory factors might modulate the function of homeodomain proteins [10].
• The histogram of neurite length of PC12 cells showed distinctive patterns on PCD that were absent on the controls [11].

Chemical compound and disease context of PCBD1

• Transforming growth factor beta 1 (TGF beta 1) and cisplatin induce apoptosis (programmed cell death, PCD) in human erythroleukemia K562 cells in an additive manner [12].
• Human neuroblastoma CHP100 cells were forced into apoptosis (programmed cell death, PCD) or necrosis by treatment with calcium chloride or sodium nitroprusside (a nitric oxide donor), respectively [13].
• Tumor necrosis factor-alpha (TNF-alpha) levels were measured in the serum (sTNF-alpha) or bone marrow (BM) biopsies of 43 patients with myelodysplastic syndromes (MDS) who subsequently received therapy with a combination of pentoxifylline and ciprofloxacin (PC) with or without dexamethasone (PCD) [14].
• One hundred and ninety-five patients with metastatic malignant melanoma were randomized to receive either cyclophosphamide 600 mg/m2 IV plus DTIC 600 mg/m2 IV day 1 (CD); or cyclophosphamide 400 mg/m2 IV, DTIC 400 mg/m2 IV, and piperazinedione 4 mg/m2 IV on day 1 (PCD) [15].
• Total 105 Japanese cases of systemic amyloidosis were analysed in terms of Congo red staining with potassium permanganate, anti-amyloid serum staining by immunoperoxidase and the occurrence of monoclonal proteins (ie. plasma cell dyscrasia, PCD) [16].

Biological context of PCBD1

• DCoHm (dimerization cofactor of hepatocyte nuclear factor 1alpha ( HNF1alpha) from muscle), a novel gene of the DCoH family with 78% amino acid identity to DCoH, was identified as a Mirk-binding protein by yeast two-hybrid analysis and cloned [1].
• The amino acid sequences of human and rat PHS/PCD were found to be identical [17].
• Genes for the dimerization cofactor of hepatocyte nuclear factor-1 alpha (DCOH) are on human and murine chromosomes 10 [18].
• The PTS gene was mapped to the chromosomal region 11q22.3-q23.3, and the PCD/DCOH gene was mapped to the 10q22 band of the genome [19].
• Using this cDNA as a probe, we isolated and determined the complete nucleotide sequence and flanking regions of the single human PCBD gene [20].

Anatomical context of PCBD1

• Earlier we have demonstrated pterin-4a-carbinolamine dehydratase (PCD) mRNA and enzyme activities in epidermal melanocytes and keratinocytes [21].
• Although the mRNA level in liver was only fourfold higher than that in keratinocytes and fibroblasts, the hepatic PCD/DCoH protein level was 20-fold higher than that in normal human epidermal keratinocytes and dermal fibroblasts [22].
• Human PCD/DCoH was present predominantly in liver and kidney, with significant amounts in testis and ovary, trace amounts in lung, and undetectable levels in whole brain, heart, and spleen [22].
• Here we report for the first time that the PCD/DCoH mRNA is present in human white blood cells and hair follicles [23].
• Human white blood cells and hair follicles are good sources of mRNA for the pterin carbinolamine dehydratase/dimerization cofactor of HNF1 for mutation detection [23].

Associations of PCBD1 with chemical compounds

• Chromosomal location of two human genes encoding tetrahydrobiopterin-metabolizing enzymes: 6-pyruvoyl-tetrahydropterin synthase maps to 11q22.3-q23.3, and pterin-4 alpha-carbinolamine dehydratase maps to 10q22 [19].
• These data show that human PCD/DCoH is not only present in cells where tetrahydrobiopterin is synthesized or HNF1 is present but is a widely distributed protein [22].
• The bifunctional protein PCD/DCoH is both an enzyme involved in the phenylalanine hydroxylation system and a transcription coactivator forming a 2:2 heterotetrameric complex with the nuclear transcription factor HNF1 [24].
• Functions attributed to erh include enhancement of pyrimidine biosynthesis, a role in cell cycle regulation, and repression of the tissue-specific transcription factor HNF-1 (hepatocyte nuclear factor-1) through binding the coactivator DCoH (dimerization cofactor of HNF1) [25].
• Hyperphenylalaninemia and impaired glucose tolerance in mice lacking the bifunctional DCoH gene [26].

Physical interactions of PCBD1

• Specific binding of DCoH/HNF-1 complex to the human tyrosinase promoter was confirmed by gel shift analysis [21].

Other interactions of PCBD1

• In situ and in vitro evidence for DCoH/HNF-1 alpha transcription of tyrosinase in human skin melanocytes [21].
• We have also used this technique to demonstrate homomeric interactions between wild-type DHPR subunits and between wild-type PCD subunits [27].
• These were 92bp upstream of SLC3A1, 52bp upstream of PCBD (DCOH), and 42202bp upstream of TCF2(HNF1-beta) [28].
• Dysfunction of DCoH/PCD is associated with the human disorders hyperphenylalaninemia and vitiligo [2].

Analytical, diagnostic and therapeutic context of PCBD1

• Using double immunofluorescence labelling, we identified that albumin colocalized together with its transcription factor PCD/DCoH/HNF-1alpha in suprabasal keratinocytes in human full-thickness skin sections and in keratinocytes cultured in serum-free medium [29].
• The relationship between the enzymatic and the transcriptional activity of the bifunctional protein pterin-4a-carbinolamine dehydratase/dimerization cofactor for hepatocyte nuclear factor 1 (DCoH) has been elucidated by site-directed mutagenesis [30].
• Immunoblotting and RT-PCR analysis for PCD/DCoH and HNF1 were also performed on both human tissues and CACO-2 and HT-29 cell lines [3].
• Crystallization and preliminary crystallographic studies of recombinant dimerization cofactor of transcription factor HNF1/pterin-4 alpha-carbinolamine dehydratase from liver [31].
• We cloned the Xenopus enhancer of rudimentary homologue (XERH) as an interaction partner of DCoH/PCD (dimerisation cofactor of HNF1/pterin-4alpha-carbinolamine dehydratase) in the yeast two-hybrid assay [32].

References