Journal
FEBS LETTERS
Volume 592, Issue 2, Pages 244-255Publisher
WILEY
DOI: 10.1002/1873-3468.12952
Keywords
class II transactivator; interferon regulatory factor 1; interferon signaling pathway; JAK/STAT pathway; NPM1; STAT1
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [24115001, 26440021, 17K07300]
- Grants-in-Aid for Scientific Research [26440021, 24115001, 17K07300] Funding Source: KAKEN
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Nucleophosmin (NPM1) is a multifunctional nucleolar protein. Here, we analyze the role of NPM1 in gene expression using our previous microarray data and find a relationship between NPM1 and interferon (IFN)-gamma-inducible genes. We show that NPM1 selectively regulates the expression of a subset of IFN-gamma-inducible genes and directly binds to two important transcription factors in the type II IFN pathway: signal transducer and activator of transcription 1 and interferon regulatory factor 1 (IRF1). Furthermore, NPM1 is found to regulate the IFN-gamma-inducible promoter activity of major histocompatibility complex class II transactivator (CIITA), and mutation of the IRF1-binding site on the CIITA promoter abolishes the effect of NPM1. Our results suggest a novel mechanism for IFN-gamma-mediated gene expression by NPM1.
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