Differential IFN-gamma stimulation of HLA-A gene expression through CRM-1-dependent nuclear RNA export.

Differential IFN-gamma stimulation of HLA-A gene expression through CRM-1-dependent nuclear RNA export. Research Abstract Details 

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Differential IFN-gamma stimulation of HLA-A gene expression through CRM-1-dependent nuclear RNA export. Abstract Text:

Sarah K Browne,James R Roesser,Sheng Zu Zhu,Gordon D Ginder,

IFNs regulate most MHC class I genes by stimulating transcription initiation. As shown previously, IFN-gamma controls HLA-A expression primarily at the posttranscriptional level. We have defined two 8-base sequences in a 39-nucleotide region in the 3'-transcribed region of the HLA-A gene that are required for the posttranscriptional response to IFN-gamma. Stimulation of HLA-A expression by IFN-gamma requires nuclear export of HLA-A mRNA by chromosome maintenance region 1 (CRM-1). Treatment of cells with leptomycin B, a specific inhibitor of CRM-1, completely inhibited IFN-gamma induction of HLA-A. Expression of a truncated, dominant-negative form of the nucleoporin NUP214/CAN, DeltaCAN, that specifically interacts with CRM-1, also prevented IFN-gamma stimulation of HLA-A, providing confirmation of the role of CRM-1. Increased expression of HLA-A induced by IFN-gamma also requires protein methylation, as shown by the fact that treatment of SK-N-MC cells or HeLa cells with the PRMT1 inhibitor 5'-methyl-5'-thioadenosine abolished the cellular response to IFN-gamma. In contrast with HLA-A, IFN-gamma-induced expression of the HLA class Ib gene, HLA-E, was not affected by either 5'-methyl-5'-thioadenosine or leptomycin B. These results provide proof of principle that it is possible to differentially modulate the IFN-gamma-induced expression of the HLA-E and HLA-A genes, whose products often mediate opposing effects on cellular immunity to tumor cells, pathogens, and autoantigens.

Differential IFN-gamma stimulation of HLA-A gene expression through CRM-1-dependent nuclear RNA export. Publishing Authors By Initials

SK Browne,JR Roesser,SZ Zhu,GD Ginder,

For similar proteins: receptors, cytoplasmic and nuclear research abstracts see: proteins: receptors, cytoplasmic and nuclear research

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Differential IFN-gamma stimulation of HLA-A gene expression through CRM-1-dependent nuclear RNA export. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 177

Page Numbers: 8612-9

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 15

MONTH: Dec

YEAR: 2006

Differential IFN-gamma stimulation of HLA-A gene expression through CRM-1-dependent nuclear RNA export. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985117

Differential IFN-gamma stimulation of HLA-A gene expression through CRM-1-dependent nuclear RNA export. Keywords Mesh Terms:

KEYWORDS: Receptors, Cytoplasmic and Nuclear

MESH TERMS: physiology

Chemical & Substance for Abstract: Differential IFN-gamma stimulation of HLA-A gene expression through CRM-1-dependent nuclear RNA export. Information

Substance Name: Interferon Type II

Registry Number: 82115-62-6

Grant and Affiliation Information for Differential IFN-gamma stimulation of HLA-A gene expression through CRM-1-dependent nuclear RNA export.

AFFILIATION: Massey Cancer Center, Virginia Commonwealth University Medical Center, 401 College Street, Richmond, VA 23298, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA 87496

ACRONYM: CA

MEDLINETA: J Immunol

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