title: The PML gene is not involved in the regulation of MHC class I expression in human cell lines.
abstract: The promyelocytic leukemia gene, PML, is a growth and transformation suppressor. An additional role for PML 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 of PML for the control MHC class I expression in human cells. PML function was perturbed in human cell lines either by PML/RAR alpha 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 dot-like 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 gamma-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.
authors.affiliation: Department of Experimental Medicine, Section of Human Anatomy, Genoa University, Genoa, Italy. silvia.bruno@unige.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Bruno
authors.forename: Fabio
authors.initials: F
authors.lastname: Ghiotto
authors.forename: Franco
authors.initials: F
authors.lastname: Fais
authors.forename: Marta
authors.initials: M
authors.lastname: Fagioli
authors.forename: Lucilla
authors.initials: L
authors.lastname: Luzi
authors.forename: Pier Giuseppe
authors.initials: PG
authors.lastname: Pelicci
authors.forename: Carlo Enrico
authors.initials: CE
authors.lastname: Grossi
authors.forename: Ermanno
authors.initials: E
authors.lastname: Ciccone
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005434:Flow Cytometry; D005799:Genes, Dominant; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000196:embryology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009447:Neuroblastoma / Q000473:pathology; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology; D015388:Organelles; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D006680:HLA Antigens; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C070576:PML protein, human; D007371:Interferon-gamma