6533b830fe1ef96bd12966a8

RESEARCH PRODUCT

A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing

Gerhard SeitzMichael PfreundschuhThomas EberleCarsten ZwickUgur SahinMichael KoslowskiMargit ZuberVillena-heinsen CPia BallweberCarolin BellBenedikt BussÖZlem Türeci

subject

Cancer ResearchLeucine zipperDNA ComplementaryTranscription GeneticGreen Fluorescent ProteinsImmunoblottingBiologymedicine.disease_causeModels BiologicalProto-Oncogene MasAntigens NeoplasmTranscription (biology)Protein targetingTumor Cells CulturedGeneticsmedicineHumansTissue DistributionAntigensMolecular BiologyGeneLeucine ZippersATF3GenomeReverse Transcriptase Polymerase Chain ReactionAlternative splicingfood and beveragesBlotting NorthernPhenotypeProtein Structure TertiaryDNA-Binding ProteinsAlternative SplicingLuminescent ProteinsPhenotypeMicroscopy FluorescenceModels ChemicalRNA splicingCancer research

description

We describe here the definition and characterization of antigen CT-8/HOM-TES-85 encoded by a previously unknown gene and identified by serological expression screening using antibodies from a seminoma patient. Intriguingly, the leucine zipper region of CT-8/HOM-TES-85 shows an atypical amphipathy with clusters of hydrophobic residues that is exclusively shared by the N-myc proto-oncogene. CT-8/HOM-TES-85 gene is tightly silenced in normal tissues except for testis. However, it is frequently activated in human neoplasms of different types including lung cancer, ovarian cancer, melanoma and glioma. Endogenous as well as heterogeneously expressed CT-8/HOM-TES-85 targets predominantly to the nucleus forming a distinctive speckled pattern of nuclear dots arranged in macromolecular structures. By co-localization studies these speckles were identified as loci of transcriptional activity and splicing, suggesting that CT-8/HOM-TES-85 may be involved in these processes. The aberrant expression of CT-8/HOM-TES-85 in human neoplasms might therefore be involved in cancer associated alterations of transcriptional or post-transcriptional processes and thus may disclose new mechanisms involved in the manifestation of the cancer phenotype.

https://doi.org/10.1038/sj.onc.1205481