Disease relevance of CDCP1

• Sequencing of a p80 cDNA established identity to CUB domain-containing protein 1 (CDCP1), a gene elevated in carcinomas [1].
• Identification of a novel gene, CDCP1, overexpressed in human colorectal cancer [2].
• CDCP1 mRNA is approximately 6 kb and highly overexpressed in human colon cancer and lung cancer [2].
• CUB-domain-containing protein 1 (CDCP1) is a novel transmembrane molecule that is expressed in metastatic colon and breast tumors as well as on the surface of hematopoietic stem cells [3].
• Transplantation of purified CDCP1(+) cells into NOD/SCID mice resulted in engraftment of human cells with multi-lineage differentiation potential, suggesting that CDCP1 is a novel marker for hematopoietic stem cells [4] .

High impact information on CDCP1

• We provide evidence that this domain mediates PKCdelta interaction with a Src binding glycoprotein, CDCP1 [5].
• CDCP1/p80 cDNA encodes three extracellular CUB domains, a transmembrane domain, and two putative cytoplasmic Tyr phosphorylation sites [1].
• Leonard Trask: the wonderful invalid: the first American description of ankylosing spondylitis [6].
• Overexpression of Trask leads to cell rounding and a loss of adhesion phenotype [7].
• Trask associates with both yes and src, is localized to the cell membrane during interphase, and undergoes cytoplasmic relocalization during mitosis [7].

Biological context of CDCP1

• CDCP1 represents a putative transmembrane protein, containing three CUB domains in the extracellular part most likely involved in cell adhesion or interacting with the extracellular matrix [2].
• The CDCP1 gene was mapped to chromosome 3p21-p23 by fluorescence in situ hybridization [2].
• In addition, CDCP1 expression on leukemic blasts and on cells with nonhematopoietic stem/progenitor cell phenotypes was determined [3].
• The in vitro methylation of CpG sites decreased CDCP1 promoter activity, and the addition of a demethylating reagent restored activity [8].
• Many CpG sequences were localized around the transcription initiation site of CDCP1 [8].

Anatomical context of CDCP1

• Immunohistochemical analysis indicated apical and basal plasma membrane expression of SIMA135/CDCP1 in epithelial cells in normal colon [9].
• In addition to high expression in M(+)HEp3 cells, the SIMA135/CDCP1 protein is expressed to varying levels in 13 other human tumor cell lines, manifesting only a weak correlation with the reported metastatic ability of these tumor cell lines [9].
• Here we demonstrate that a subset of bone marrow (BM), cord blood (CB), and mobilized peripheral blood (PB) CD34+ cells expressed this marker and that CDCP1 was detected on CD34(+)CD38- BM stem/progenitor cells but not on mature PB cells [3].
• CDCP1 mRNA is highly expressed in lung and colon tumors and in the erythroleukemic cell line K562 [4].
• CDCP1 is a novel marker for hematopoietic stem cells [4].
• Adhesion or plasmin regulates tyrosine phosphorylation of a novel membrane glycoprotein p80/gp140/CUB domain-containing protein 1 in epithelia [1] .

Physical interactions of CDCP1

• Addition of demethylating reagent to Jurkat induced CDCP1 expression, and increased the zfp67 binding to CDCP1 promoter [10].

Other interactions of CDCP1

• CDCP1 identifies a broad spectrum of normal and malignant stem/progenitor cell subsets of hematopoietic and nonhematopoietic origin [3].
• However, CDCP1 was not strictly correlated with CD34 and/or CD133 expression, suggesting that CDCP1 is a novel marker for leukemia diagnosis [3].
• Tumours with high-level CDCP1 expression showed higher levels of proliferation, as revealed by immunohistochemical detection of the MIB-1 antigen, than tumours with low-level CDCP1 expression [8].
• The reporter assay and si-RNA-mediated knockdown experiment revealed that zfp67, a zinc-finger protein, enhanced CDCP1 transcription [10].

Analytical, diagnostic and therapeutic context of CDCP1

• Protein sequence analysis predicted a cell surface location and type I orientation of SIMA135/CDCP1, which was confirmed directly by immunocytochemistry [9].
• In this study, we used multiparameter flow cytometry and antibodies against CDCP1 to analyze the expression of CDCP1 on defined hematopoietic cell subsets of different sources [3].
• Amount of zfp67 in Jurkat was comparable with K562, but chromatin immunoprecipitation showed that zfp67 bound to CDCP1 promoter in K562 but not in Jurkat [10].
• Northern blot analysis indicated that SIMA135/CDCP1 mRNA has a restricted expression pattern in normal human tissues with highest levels of expression in skeletal muscle and colon [9].
• Western blot analysis using a antiphosphotyrosine antibody demonstrated that SIMA135/CDCP1 from HEp3 cells is tyrosine phosphorylated [9].

References