The PML gene is not involved in the regulation of MHC class I expression in human cell lines

• Published in: Blood Vol. 101; no. 9; pp. 3514 - 3519
• Main Authors: Bruno, Silvia, Ghiotto, Fabio, Fais, Franco, Fagioli, Marta, Luzi, Lucilla, Pelicci, Pier Giuseppe, Grossi, Carlo Enrico, Ciccone, Ermanno
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-05-2003; The Americain Society of Hematology
• Subjects: Amino Acid Sequence; Animals; Antigens; Biological and medical sciences; Cell Line; Cytoplasm - metabolism; Exons - genetics; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes, Dominant; Genes, MHC Class I; HeLa Cells; Hematologic and hematopoietic diseases; Histocompatibility antigens (hla, h-2 and other systems); HLA Antigens - biosynthesis; HLA Antigens - genetics; Humans; Interferon-gamma - pharmacology; Kidney - cytology; Kidney - embryology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Mice; Molecular immunology; Molecular Sequence Data; Mutation; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Neuroblastoma - pathology; Nuclear Proteins; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - physiology; Organelles; Promyelocytic Leukemia Protein; Protein Isoforms - genetics; Protein Isoforms - physiology; Recombinant Fusion Proteins - physiology; RNA Interference; Sequence Alignment; Sequence Homology, Amino Acid; Transcription Factors - genetics; Transcription Factors - physiology; Transfection; Tumor Cells, Cultured; Tumor Suppressor Proteins; Human; Promyelocytic leukemia; Acute; Major histocompatibility system; Malignant hemopathy; Hela cell line; Regulation(control); Cell line; Gene; Chromosome E17; Chromosome D15; Established cell line; Genetics; Class I histocompatibility antigen
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-11-3335

The promyelocytic leukemia gene, PML, is a growth and transformation suppressor. An additional role forPML as a regulator of major histocompatibility complex (MHC) class I antigen presentation has been proposed in a murine model, which would account for evasion from host immunity of tumors bearing malfunctioning PML, such as acute promyelocytic leukemia. Here we investigated a possible role ofPML for the control MHC class I expression in human cells. PML function was perturbed in human cell lines either byPML/RARα transfection or by PML- specific RNA interference. Impairment of wild-type PML function was proved by a microspeckled disassembly of nuclear bodies (NBs), where the protein is normally localized, or by their complete disappearance. However, no MHC class I down-regulation was observed in both instances. We next constructed a PML mutant, PML mut ex3,that is a human homolog of the murine PML mutant, truncated in exon 3, that was shown to down-regulate murine MHC class I. PML mut ex3 transfected in human cell lines exerted a dominant-negative effect since no PML molecules were detected in NBs but, instead, in perinuclear and cytoplasmic larger dotlike structures. Nevertheless, no down-regulation of MHC class I expression was evident. Moreover, neither transfection with PML mut ex3 nor PML-specific RNA interference affected the ability of γ-interferon to up-regulate MHC class I expression. We conclude that, in human cell lines, PML is not involved directly in the regulation of MHC class I expression.