Disease relevance of CITED1

• Among non-neoplastic thyroids, adenomatous hyperplasia frequently expressed GAL3 (n=16), CK19 (n=9) and CITED1 (n=7), but the expression was predominantly focal in contrast to the diffuse expression in carcinomas [1].
• Expression of msg1 was undetectable in the amelanotic K1735 murine melanoma cells [2].
• Intracellularly, MSG1 protein was localized in the cytoplasm of nevus cells, but was seen in both nuclei and cytoplasm of melanoma cells [3].
• Normal thyroids (n = 27), thyrotoxic hyperplasias (n = 14), and anaplastic thyroid carcinomas (n = 5) did not express CITED1 [4].
• CITED1 expression was seen in 63 of 68 PTC (93%), 3 of 12 follicular carcinomas (25%), 2 of 7 Hürthle cell carcinomas (28%), 2 of 21 adenomas (10%), 2 of 6 follicular neoplasms of undetermined malignant behavior (33%), and 2 of 24 nodular goiters (8%) [4].

High impact information on CITED1

• An expanded peripheral T cell population to a cytotoxic T lymphocyte (CTL)-defined, melanocyte-specific antigen in metastatic melanoma patients impacts on generation of peptide-specific CTLs but does not overcome tumor escape from immune surveillance in metastatic lesions [5].
• High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo [6].
• It has recently been suggested that reverse transcription and polymerase chain reaction (RT-PCR)-based detection of tyrosinase messenger RNA (mRNA) in peripheral blood might be useful in the early detection of circulating tumor cells, since tyrosinase is thought to be a melanocyte-specific marker [7].
• Analysis of a melanocyte-specific phenotype marker (MART-1) and a neuronal marker (Tuj1) revealed a subpopulation of melanoma cells that invade the chick periphery and express MART-1 and Tuj1 [8].
• Immunohistochemical analysis detected CITED1 and SFTPB in 49/52 and 39/52 PTCs, respectively, but not in follicular thyroid carcinoma and normal thyroid tissue [9].

Chemical compound and disease context of CITED1

• Identification of a secreted Mr 95,000 glycoprotein in human melanocytes and melanomas by a melanocyte specific monoclonal antibody [10].

Biological context of CITED1

• The Transcriptional Activity of CITED1 Is Regulated by Phosphorylation in a Cell Cycle-dependent Manner [11].
• In the present study, we show that the phosphorylation status of CITED1 changes during the cell cycle and affects its transcriptional cofactor activity [11].
• Tryptic mapping and mutagenesis studies identified five phosphorylated serine residues in CITED1 [11].
• Transformation of murine melanocytes by transfection with v-Ha-ras or Ela was accompanied by depigmentation and led to complete loss of msg1 expression [2].
• The normal tissue distribution of msg1 mRNA transcripts in adult mice was confined to melanocytes and testis [2].

Anatomical context of CITED1

• The pigmented murine melanocyte cell line melan-a expressed msg1, as did pigmented primary cultures of murine and human melanocytes; however, seven amelanotic or very weakly pigmented human melanoma cell lines were negative [2].
• The CITED1 protein, a 27-kd transcriptional transactivator nuclear protein is expressed in PTC, melanocytes, breast epithelial cells, and several embryonic tissues [4].
• The MSG1 (melanocyte-specific gene 1), a gene originally isolated from melanocytes and containing a strong transcription activation domain, was also found expressed in all melanomas and most non-melanocyte tumor cell lines [12].
• Here, we show that AP-3 and AP-1 function independently in sorting of the melanocyte-specific protein tyrosinase from endosomes to the melanosome, a specialized lysosome-related organelle distinguishable from lysosomes [13].
• We propose that in the melanocyte, the HPS gene product regulates in part the trafficking of melanocyte-specific proteins from the trans-Golgi network to preformed premelanosomes [14].

Associations of CITED1 with chemical compounds

• The authors have previously shown that an RT-PCR assay designed to detect melanocyte-specific expression of the tyrosinase gene could be used to define a population of patients at higher risk for both recurrence and death compared with routine hematoxylin and eosin (H&E) histology [15].
• Tyrosinase is a melanocyte specific copper-containing enzyme that catalyzes the conversion of the amino acid tyrosine, through a complex series of intermediates, to melanin [16].
• However, over this same pH range, if various metals or a melanocyte-specific enzyme are present, it rapidly rearranges to its isomer form--5,6-dihydroxyindole-2-carboxylic acid (DHICA)--which is far more stable than dopachrome in its ability to retain the carboxyl group [17].
• Tyrosinase-related protein-2 (TYRP2) is a melanocyte-specific enzyme that catalyses the non-decarboxylative tautomerization of L-dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in the melanin biosynthetic pathway [18].

Physical interactions of CITED1

• The C-terminal transactivating domain of MSG1 is required for binding to p300/CBP and enhancement of Smad-mediated transcription; the viral VP16 transactivating domain could not substitute for it [19].

Regulatory relationships of CITED1

• When cotransfected, MSG1 enhances transcription mediated by the Smad transcription factors in mammalian cells in a manner dependent on ligand-induced Smad hetero-oligomerization [19].
• Pax3 transcription factor was reported earlier to regulate positively the melanocyte-specific promoter of the MITF gene [12].
• The MSG1 mRNA transcripts were rapidly induced by either endothelin-1 or TPA [20].
• Microphthalmia-associated transcription factor (MITF) activates the expression of melanocyte-specific markers and promotes the survival of embryonic, adult and malignant melanocytes [21].
• The detection of tyrosinase mRNA-positive circulating melanoma cells by reverse transcription-polymerase chain reaction (RT-PCR) has been limited to disseminated tumours expressing measurable amounts of this melanocyte-specific enzyme [22].

Other interactions of CITED1

• GAL3 and CITED1, less useful individually, could help in selective cases [23].
• Together, these data indicate that the MITF-M isoform is the major type of MITF mRNA present in human melanoma cell lines and show that the expression of the isoform MITF-A and the MSG1 is not restricted to malignant melanocytes and occurs in a wide range of tumor cell lines [12].
• Expression of genes for microphthalmia isoforms, Pax3 and MSG1, in human melanomas [12].
• Melanocyte-specific gene expression: role of repression and identification of a melanocyte-specific factor, MSF [24].
• A yeast two-hybrid screen identified the recently described melanocyte-specific gene-related gene 1 (MRG1) as an Lhx2 LIM-interacting protein [25].

Analytical, diagnostic and therapeutic context of CITED1

• The msg1 protein was localized to the melanocyte nucleus by immunofluorescence cytochemistry [2].
• In this study, we analyzed MSG1 protein expression by immunohistochemistry using human tumor samples from nevus and malignant melanoma to reveal its role in pigmentation and melanoma development in vivo [3].
• Southern blot analysis suggests the existence of MSG1 homologues in chicken, zebrafish, and Drosophila [26].
• STUDY SELECTION AND DATA EXTRACTION: Cited studies were critically reviewed with emphasis on study size, patient sample, methods, diagnostic criteria, and reproducibility of results [27].
• The exclusively melanocyte-specific tyrosinase transcript was amplified by reverse transcription followed by polymerase chain reaction (RT-PCR) [28].

References