A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing.
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.
Türeci
Ozlem
O
III. Medizinische Klinik und Poliklinik, Johannes Gutenberg Universität Mainz, D-55131 Mainz, Germany.
Sahin
Ugur
U
Koslowski
Michael
M
Buss
Benedikt
B
Bell
Carolin
C
Ballweber
Pia
P
Zwick
Carsten
C
Eberle
Thomas
T
Zuber
Margit
M
Villena-Heinsen
Carlos
C
Seitz
Gerhard
G
Pfreundschuh
Michael
M
D017398:Alternative Splicing; D000941:Antigens / Q000737:chemistry* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D015152:Blotting, Northern; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D016678:Genome; D049452:Green Fluorescent Proteins; D006801:Humans; D015151:Immunoblotting; D016350:Leucine Zippers; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008956:Models, Chemical; D010641:Phenotype; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000941:Antigens; D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C456621:LUZP4 protein, human; D008164:Luminescent Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D049452:Green Fluorescent Proteins