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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-11-3335.
Submitted November 5, 2002
Accepted December 10, 2002
The PML gene is not involved in the regulation of MHC class I expression in human cell lines
Silvia Bruno*, Fabio Ghiotto, Franco Fais, Marta Fagioli, Lucilla Luzi, Pier Giuseppe Pelicci, Carlo Enrico Grossi, and Ermanno Ciccone
Department of Experimental Medicine - Section of Human Anatomy, University of Genoa, Genoa, Italy
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
Department of Clinical and Experimental Medicine - Section of Internal Medicine and Oncological Sciences, University of Perugia, Perugia, Italy
Institute for Molecular Oncology, Fondazione Italiana per la Ricerca sul Cancro, Milan, Italy
* Corresponding author; email: Silvia.Bruno{at}unige.it.
The promyelocytic leukemia gene, PML, is a growth and transformation suppressor. Recently, an additional role for PML as a regulator of MHC class I antigen presentation has been proposed in a murine model (Zheng et al., Nature, 396:373,1998). This role would account for evasion from host immunity of tumors bearing malfunctioning PML, such as acute promyelocytic leukemia (APL). Here we investigated whether or not PML controls MHC class I expression also in human cells. The function of PML was affected in human cell lines either by PML/RAR or by PML-specific RNA interference. The impairment of PML wt function was proven by microspeckled disassembly of nuclear bodies (NB), where the protein is normally localized, or by their complete disappearance, respectively. However, no MHC class I reduction was observed in both cases. We then constructed a PML mutant, called 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 (paper cited above). PML mut ex3 transfected in human cell lines exerted a dominant negative action, since no PML molecules were detected in NB, but instead in perinuclear and cytoplasmic larger dot-like structures. Nevertheless, no down-regulation of MHC class I expression was found. Moreover, neither transfection with PML mut ex3 nor PML-specific RNA interference, affected the ability of  -interferon to up-regulate MHC class I expression. We conclude that, in human cell lines, PML is not directly involved in the regulation of MHC class I expression.
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