Dataset Information

Interferon gamma is recognised by importin alpha/beta: enhanced nuclear localising and transactivation activities of an interferon gamma mimetic.

ABSTRACT: Interferon (IFN) gamma's ability to localise in the nucleus and function in gene activation has been known for some time, although the role of the conventional nuclear transporting importin molecules is unclear. Here, we demonstrate for the first time the direct recognition of IFNgamma and an IFNgamma mimetic peptide by IMPalpha and the IMPalpha/beta heterodimer, where the IFNgamma mimetic shows higher affinity. Significantly, this correlates well both with in vivo ability to target green fluorescent protein to the nucleus in transfected cells as determined by quantitative confocal laser scanning microscopy, as well as GAS promoter activity of a luciferase reporter. This has important implications for IFNgamma's anti-viral action, and the potential use of the IFNgamma mimetic in antiviral therapies.

SUBMITTER: Fulcher AJ

PROVIDER: S-EPMC2689648 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interferon gamma is recognised by importin alpha/beta: enhanced nuclear localising and transactivation activities of an interferon gamma mimetic.

Fulcher Alex J AJ Ahmed Chulbul M I CM Noon-Song Ezra N EN Kwan Rain Y Q RY Subramaniam Prem S PS Johnson Howard M HM Jans David A DA

FEBS letters 20080409 11

Interferon (IFN) gamma's ability to localise in the nucleus and function in gene activation has been known for some time, although the role of the conventional nuclear transporting importin molecules is unclear. Here, we demonstrate for the first time the direct recognition of IFNgamma and an IFNgamma mimetic peptide by IMPalpha and the IMPalpha/beta heterodimer, where the IFNgamma mimetic shows higher affinity. Significantly, this correlates well both with in vivo ability to target green fluore ...[more]

PMID: 18405666

Similar Datasets

Project description:Rabies virus P-protein is expressed as five isoforms (P1-P5) which undergo nucleocytoplasmic trafficking important to roles in immune evasion. Although nuclear import of P3 is known to be mediated by an importin (IMP)-recognised nuclear localization sequence in the N-terminal region (N-NLS), the mechanisms underlying nuclear import of other P isoforms in which the N-NLS is inactive or has been deleted have remained unresolved. Based on the previous observation that mutation of basic residues K214/R260 of the P-protein C-terminal domain (P-CTD) can result in nuclear exclusion of P3, we used live cell imaging, protein interaction analysis and in vitro nuclear transport assays to examine in detail the nuclear trafficking properties of this domain. We find that the effect of mutation of K214/R260 on P3 is largely dependent on nuclear export, suggesting that nuclear exclusion of mutated P3 involves the P-CTD-localized nuclear export sequence (C-NES). However, assays using cells in which nuclear export is pharmacologically inhibited indicate that these mutations significantly inhibit P3 nuclear accumulation and, importantly, prevent nuclear accumulation of P1, suggestive of effects on NLS-mediated import activity in these isoforms. Consistent with this, molecular binding and transport assays indicate that the P-CTD mediates IMP?2/IMP?1-dependent nuclear import by conferring direct binding to the IMP?2/IMP?1 heterodimer, as well as to a truncated form of IMP?2 lacking the IMP?-binding autoinhibitory domain (?IBB-IMP?2), and IMP?1 alone. These properties are all dependent on K214 and R260. This provides the first evidence that P-CTD contains a genuine IMP-binding NLS, and establishes the mechanism by which P-protein isoforms other than P3 can be imported to the nucleus. These data underpin a refined model for P-protein trafficking that involves the concerted action of multiple NESs and IMP-binding NLSs, and highlight the intricate regulation of P-protein subcellular localization, consistent with important roles in infection.

Dataset Information

Interferon gamma is recognised by importin alpha/beta: enhanced nuclear localising and transactivation activities of an interferon gamma mimetic.

Publications

Interferon gamma is recognised by importin alpha/beta: enhanced nuclear localising and transactivation activities of an interferon gamma mimetic.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets