Interferon-Modulated Expression of Genes Encoding the Nuclear-Dot-Associated Proteins Sp100 and Promyelocytic Leukemia Protein (PML)

Authors


H. Will, Heinrich-Pette-Institut, Martinistr. 52, D-20251 Hamburg, Germany
Fax: +49 40 48051221.

Abstract

Promyelocytic leukemia protein (PML) and Sp100 are transcription-regulatory proteins which colocalize in discrete nuclear dots and play a role in autoimmunity, oncogenesis and virus-host interaction. Interferons (IFNs) were shown previously to increase strongly the levels of Sp100 mRNA and protein. Here, we examined which mechanisms lead to upregulation of Sp100 gene expression and whether IFNs also increase expression of the promyelocytic leukemia (PML) gene. We found that both mRNA and protein levels of PML are also strongly upregulated by IFNs. In addition, new Sp100 and PML proteins were detected immunologically after IFN treatment of cells. Nuclear run-on analysis revealed protein-synthesis-independent, rapid IFN-enhanced transcription rates as well as synergistic activation of the Sp100 and PML genes by type-I and type-II IFNs. These data demonstrate that PML and Sp100 belong to the growing family of IFN-stimulated genes (ISGs) upregulated most likely by the transcription factor ISGF3, and indicate that IFNs also qualitatively alter the expression of these two genes.

Abbreviations
APL

acute promyelocytic leukemia

GAF

interferon γ activation factor

GAS

interferon γ activation site

GBP-1

guanylate-binding protein 1

GraP -DH

glyceraldehyde-3-phosphate dehydrogenase

HSV-1

herpes simplex virus 1

IFN

interferon

ISG

interferon-stimulated gene

ISGF3

interferon-stimulated gene factor 3

ISRE

interferon-stimulated response element

ND

nuclear dot

NDP52

nuclear dot protein 52

PBC

primary biliary cirrhosis

PML

promyelocytic leukemia protein

RARα

retinoic acid receptor α

STAT

signal transducer and activator of transcription

Enzymes
 

Horseradish peroxidase (EC 1.11.1.7)

 

glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12)

Ancillary