TY - JOUR
T1 - The PML gene is not involved in the regulation of MHC class I expression in human cell lines
AU - Bruno, Silvia
AU - Ghiotto, Fabio
AU - Fais, Franco
AU - Fagioli, Marta
AU - Luzi, Lucilla
AU - Pelicci, Pier Giuseppe
AU - Grossi, Carlo Enrico
AU - Ciccone, Ermanno
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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/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 mute 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.
AB - 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/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 mute 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.
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U2 - 10.1182/blood-2002-11-3335
DO - 10.1182/blood-2002-11-3335
M3 - Article
C2 - 12506025
AN - SCOPUS:0037866466
VL - 101
SP - 3514
EP - 3519
JO - Blood
JF - Blood
SN - 0006-4971
IS - 9
ER -