Journal article
Identification of a Nuclear Export Sequence in the MHC CIITA
The Journal of immunology (1950), v 194(12), pp 6102-6111
15 Jun 2015
PMID: 25948812
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Initiation of an immune response through expression of MHC class II and related genes is under the control of the CIITA. Normally found in both the cytoplasm and nucleus, CIITA is tightly controlled by a variety of posttranslational modifications as well as interactions with other nuclear and cytoplasmic factors, whereas disruption of this dual subcellular localization impairs CIITA functioning and expression of target genes. Although CIITA has well-defined domains necessary for its nuclear import, the region responsible for the translocation of CIITA from the nucleus has not been characterized. In this study, we identify a leucine-rich motif at residues 717-724 that bears strong homology to known nuclear export sequence (NES) domains. Mutation of this region renders CIITA insensitive to treatment with leptomycin B, an inhibitor of nuclear export, whereas fusion of this domain to a heterologous GFP is sufficient to induce its export to the cytoplasm or cause its retention in the nucleus following leptomycin B treatment. Point mutations of specific leucine residues within the NES disrupt the normal subcellular distribution of the full-length CIITA, impair its ability to interact with the nuclear export factor CRM1, and enhance CIITA-induced gene expression from an MHC class II gene promoter. IFN-gamma stimulation of class II genes is further enhanced by inhibiting the nuclear export of endogenous CIITA. Collectively, these data demonstrate the first identification of a specific NES within CIITA and place it among the other protein domains that contribute to the posttranslational regulation of CIITA activity.
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Details
- Title
- Identification of a Nuclear Export Sequence in the MHC CIITA
- Creators
- Emily Chiu - Sarah Lawrence CollegeTheresa Gold - Sarah Lawrence CollegeVeronica Fettig - Sarah Lawrence CollegeMichael T. LeVasseur - Sarah Lawrence CollegeDrew E. Cressman - Sarah Lawrence College
- Publication Details
- The Journal of immunology (1950), v 194(12), pp 6102-6111
- Publisher
- Amer Assoc Immunologists
- Number of pages
- 10
- Grant note
- Sherman Fairchild Foundation MCB0515853 / National Science Foundation; National Science Foundation (NSF) Hearst Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Epidemiology and Biostatistics
- Web of Science ID
- WOS:000355757800055
- Scopus ID
- 2-s2.0-84931459116
- Other Identifier
- 991021448184004721
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- Web of Science research areas
- Immunology