ABSTRACT
Polyfunctional protein PML contributes significantly in vital activity of cell. 11 isoforms of PML differ from one another by C-terminal domain. In spite of intensive research into the protein, the role of the isoforms in cellular processes remains obscure. In addition, the literature contains various names of the isoforms. The goal of this work was to review the structure of the PML gene, variants of alternative splicing of mPNA, and domain organization of corresponding protein forms. The PML isoforms were classified and functional specificity of each PML isoform was characterized: contribution to gene transcription, contribution to cell apoptosis, cell growth, immune response, formation of nuclear bodies.
Subject(s)
Alternative Splicing , Gene Expression Regulation, Leukemic , Leukemia, Promyelocytic, Acute/genetics , Nuclear Proteins/classification , Nuclear Proteins/genetics , Transcription Factors/classification , Transcription Factors/genetics , Tumor Suppressor Proteins/classification , Tumor Suppressor Proteins/genetics , Zinc Fingers , Animals , Apoptosis/genetics , Cell Growth Processes/genetics , Cell Nucleus/metabolism , Humans , Nuclear Proteins/metabolism , Promyelocytic Leukemia Protein , Protein Isoforms/classification , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Structure, Tertiary/physiology , Transcription Factors/metabolism , Tumor Suppressor Proteins/metabolismABSTRACT
Survivin (BIRC5) is one of the members of IAP-family apoptosis inhibitors. The BIRCS gene is expressed in most human embryonic tissues and malignant tumors but not in normal differentiated tissues of adult human. It was suggested that BIRC5 proteins inhibit apoptosis and play an essential role in tumorigenesis, makings surviving an attractive target for anticancer therapy. The mechanisms regulating level of survivin are not completely understood. It was supposed that natural inhibitors of survivin, namely SMAC and PML, play an important role in these processes. Using RT-PCR and immunoblotting we analyzed the transcription level of BIRC5, SMAC and PML genes and content of corresponding proteins in normal and tumor human tissues in non-small cell lung cancer and esophageal squamous cell carcinoma. It was demonstrated that BIRC5 is transcribed only in tumor tissues, whereas expression levels of SMAC and PML are the same in normal and tumor tissues. The contents of proteins correspond to levels of mRNA of the respective genes. Thus the increase of level of survivin in tumor tissues is not the result of decrease in content of its inhibitors SMAC and PML, as their content in tumor and normal cells is the same.
