scholarly journals Nuclear export of actin: a novel mechanism regulating the subcellular localization of a major cytoskeletal protein

1998 ◽  
Vol 17 (6) ◽  
pp. 1635-1641 ◽  
Author(s):  
A. Wada
Keyword(s):  
Subcellular Localization ◽  
Nuclear Export ◽  
Cytoskeletal Protein

scholarly journals Regulation of NT-PGC-1α Subcellular Localization and Function by Protein Kinase A-dependent Modulation of Nuclear Export by CRM1

2010 ◽  
Vol 285 (23) ◽  
pp. 18039-18050 ◽  
Author(s):  
Ji Suk Chang ◽  
Peter Huypens ◽  
Yubin Zhang ◽  
Chelsea Black ◽  
Anastasia Kralli ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Subcellular Localization ◽  
Protein Kinase A ◽  
Nuclear Export ◽  
And Function ◽  
Kinase A

CRM1-dependent nuclear export and dimerization with hMSH5 contribute to the regulation of hMSH4 subcellular localization

2007 ◽  
Vol 313 (17) ◽  
pp. 3680-3693 ◽  
Author(s):  
Sophie Neyton ◽  
Françoise Lespinasse ◽  
François Lahaye ◽  
Pascal Staccini ◽  
Véronique Paquis-Flucklinger ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Nuclear Export

scholarly journals Identification of the Nuclear Export and Adjacent Nuclear Localization Signals for ORF45 of Kaposi's Sarcoma-Associated Herpesvirus

2008 ◽  
Vol 83 (6) ◽  
pp. 2531-2539 ◽  
Author(s):  
Xiaojuan Li ◽  
Fanxiu Zhu
Keyword(s):  
Subcellular Localization ◽  
Nuclear Localization ◽  
Nuclear Export ◽  
Kaposi's Sarcoma ◽  
Nuclear Export Signal ◽  
Kaposi’S Sarcoma ◽  
Lytic Replication ◽  
Wild Type ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Open reading frame 45 (ORF45) of Kaposi's sarcoma-associated herpesvirus 8 (KSHV) is an immediate-early phosphorylated tegument protein and has been shown to play important roles at both early and late stages of viral infection. Homologues of ORF45 exist only in gammaherpesviruses, and their homology is limited. These homologues differ in their protein lengths and subcellular localizations. We and others have reported that KSHV ORF45 is localized predominantly in the cytoplasm, whereas its homologue in murine herpesvirus 68 is localized exclusively in the nucleus. We observed that ORF45s of rhesus rhadinovirus and herpesvirus saimiri are found exclusively in the nucleus. As a first step toward understanding the mechanism underlying the distinct intracellular distribution of KSHV ORF45, we identified the signals that control its subcellular localization. We found that KSHV ORF45 accumulated rapidly in the nucleus in the presence of leptomycin B, an inhibitor of CRM1 (exportin 1)-dependent nuclear export, suggesting that it could shuttle between the nucleus and cytoplasm. Mutational analysis revealed that KSHV ORF45 contains a CRM1-dependent, leucine-rich-like nuclear export signal and an adjacent nuclear localization signal. Replacement of the key residues with alanines in these motifs of ORF45 disrupts its shuttling between the cytoplasm and nucleus. The resulting ORF45 mutants have restricted subcellular localizations, being found exclusively either in the cytoplasm or in the nucleus. Recombinant viruses were reconstituted by introduction of these mutations into KSHV bacterial artificial chromosome BAC36. The resultant viruses have distinct phenotypes. A mutant virus in which ORF45 is restricted to the cytoplasm behaves as an ORF45-null mutant and produces 5- to 10-fold fewer progeny viruses than the wild type. In contrast, mutants in which the ORF45 protein is mostly restricted to the nucleus produce numbers of progeny viruses similar to those produced by the wild type. These data suggest that the subcellular localization signals of ORF45 have important functional roles in KSHV lytic replication.

scholarly journals Distinct Subcellular Localization Patterns Contribute to Functional Specificity of the Cln2 and Cln3 Cyclins of Saccharomyces cerevisiae

2000 ◽  
Vol 20 (2) ◽  
pp. 542-555 ◽  
Author(s):  
Mary E. Miller ◽  
Frederick R. Cross
Keyword(s):  
Cell Cycle ◽  
Subcellular Localization ◽  
Nuclear Localization ◽  
Nuclear Export ◽  
Cytoplasmic Localization ◽  
Cyclin Dependent Kinase ◽  
Functional Profile ◽  
Functional Specificity ◽  
Biochemical Fractionation ◽  
Nuclear Events

ABSTRACT The G1 cyclins of budding yeast drive cell cycle initiation by different mechanisms, but the molecular basis of their specificity is unknown. Here we test the hypothesis that the functional specificity of G1 cyclins is due to differential subcellular localization. As shown by indirect immunofluorescence and biochemical fractionation, Cln3p localization appears to be primarily nuclear, with the most obvious accumulation of Cln3p to the nuclei of large budded cells. In contrast, Cln2p localizes to the cytoplasm. We were able to shift localization patterns of truncated Cln3p by the addition of nuclear localization and nuclear export signals, and we found that nuclear localization drives a Cln3p-like functional profile, while cytoplasmic localization leads to a partial shift to a Cln2p-like functional profile. Therefore, forcing Cln3p into a Cln2p-like cytoplasmic localization pattern partially alters the functional specificity of Cln3p toward that of Cln2p. These results suggest that there are CLN-dependent cytoplasmic and nuclear events important for cell cycle initiation. This is the first indication of a cytoplasmic function for a cyclin-dependent kinase. The data presented here support the idea that cyclin function is regulated at the level of subcellular localization and that subcellular localization contributes to the functional specificity of Cln2p and Cln3p.

scholarly journals Nonmuscle Myosin Promotes Cytoplasmic Localization of PBX

2003 ◽  
Vol 23 (10) ◽  
pp. 3636-3645 ◽  
Author(s):  
He Huang ◽  
Miltiadis Paliouras ◽  
Isabel Rambaldi ◽  
Paul Lasko ◽  
Mark Featherstone
Keyword(s):  
Subcellular Localization ◽  
Heavy Chain ◽  
Nuclear Export ◽  
Coiled Coil ◽  
Limb Bud ◽  
Nonmuscle Myosin ◽  
Interaction Domain ◽  
Nuclear Localization Signals ◽  
Nonmuscle Myosin Ii ◽  
Coil Structure

ABSTRACT In the absence of MEIS family proteins, two mechanisms are known to restrict the PBX family of homeodomain (HD) transcription factors to the cytoplasm. First, PBX is actively exported from the nucleus via a CRM1-dependent pathway. Second, nuclear localization signals (NLSs) within the PBX HD are masked by intramolecular contacts. In a screen to identify additional proteins directing PBX subcellular localization, we identified a fragment of murine nonmuscle myosin II heavy chain B (NMHCB). The interaction of NMHCB with PBX was verified by coimmunoprecipitation, and immunofluorescence staining revealed colocalization of NMHCB with cytoplasmic PBX in the mouse embryo distal limb bud. The interaction domain in PBX mapped to a conserved PBC-B region harboring a potential coiled-coil structure. In support of the cytoplasmic retention function, the NMHCB fragment competes with MEIS1A to redirect PBX, and the fly PBX homologue EXD, to the cytoplasm of mammalian and insect cells. Interestingly, MEIS1A also localizes to the cytoplasm in the presence of the NMHCB fragment. These activities are largely independent of nuclear export. We show further that the subcellular localization of EXD is deregulated in Drosophila zipper mutants that are depleted of nonmuscle myosin heavy chain. This study reveals a novel and evolutionarily conserved mechanism controlling the subcellular distribution of PBX and EXD proteins.

scholarly journals Subcellular localization and secretion of activity-dependent neuroprotective protein in astrocytes

2004 ◽  
Vol 1 (3) ◽  
pp. 193-199 ◽  
Author(s):  
SHARON FURMAN ◽  
RUTH A. STEINGART ◽  
SHMUEL MANDEL ◽  
JANET M. HAUSER ◽  
DOUGLAS E. BRENNEMAN ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Cell Fractionation ◽  
Amino Acid Peptide ◽  
Extracellular Milieu ◽  
Domain Profile ◽  
Localization Signal ◽  
Developing Neurons ◽  
Activity Dependent

Activity-dependent neuroprotective protein (ADNP, ∼123562.8 Da), is synthesized in astrocytes and expression of ADNP mRNA is regulated by the neuroprotective peptide vasoactive intestinal peptide (VIP). The gene that encodes ADNP is conserved in human, rat and mouse, and contains a homeobox domain profile that includes a nuclear-export signal and a nuclear-localization signal. ADNP is essential for embryonic brain development, and NAP, an eight-amino acid peptide that is derived from ADNP, confers potent neuroprotection. Here, we investigate the subcellular localization of ADNP through cell fractionation, gel electrophoresis, immunoblotting and immunocytochemistry using α-CNAP, an antibody directed to the neuroprotective NAP fragment that constitutes part of an N-terminal epitope of ADNP. Recombinant ADNP was used as a competitive ligand to measure antibody specificity. ADNP-like immunoreactivity was found in the nuclear cell fraction of astrocytes and in the cytoplasm. In the cytoplasm, ADNP-like immunoreactivity colocalized with tubulin-like immunoreactivity and with microtubular structures, but not with actin microfilaments. Because microtubules are key components of developing neurons and brain, possible interaction between tubulin and ADNP might indicate a functional correlate to the role of ADNP in the brain. In addition, ADNP-like immunoreactivity in the extracellular milieu of astrocytes increased by ∼1.4 fold after incubation of the astrocytes with VIP. VIP is known to cause astrocytes to secrete neuroprotective/neurotrophic factors, and we suggest that ADNP constitutes part of this VIP-stimulated protective milieu.

scholarly journals Subcellular localization of full-length human myeloid leukemia factor 1 (MLF1) is independent of 14-3-3 proteins

2013 ◽  
Vol 18 (1) ◽  
Author(s):  
Manuela Molzan ◽  
Christian Ottmann
Keyword(s):  
Subcellular Localization ◽  
Nuclear Export ◽  
Myeloid Leukemia ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Physiological Function ◽  
Full Length ◽  
Interaction Partners ◽  
Functional Features ◽  
Nuclear Localization Sequences

AbstractMyeloid leukemia factor 1 (MLF1) is associated with the development of leukemic diseases such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, information on the physiological function of MLF1 is limited and mostly derived from studies identifying MLF1 interaction partners like CSN3, MLF1IP, MADM, Manp and the 14-3-3 proteins. The 14-3-3-binding site surrounding S34 is one of the only known functional features of the MLF1 sequence, along with one nuclear export sequence (NES) and two nuclear localization sequences (NLS). It was recently shown that the subcellular localization of mouse MLF1 is dependent on 14-3-3 proteins. Based on these findings, we investigated whether the subcellular localization of human MLF1 was also directly 14-3-3-dependent. Live cell imaging with GFP-fused human MLF1 was used to study the effects of mutations and deletions on its subcellular localization. Surprisingly, we found that the subcellular localization of full-length human MLF1 is 14-3-3-independent, and is probably regulated by other as-yet-unknown proteins.

scholarly journals Subcellular localization of CrmA: identification of a novel leucine-rich nuclear export signal conserved in anti-apoptotic serpins

2003 ◽  
Vol 373 (1) ◽  
pp. 251-259 ◽  
Author(s):  
Jose A. RODRIGUEZ ◽  
Simone W. SPAN ◽  
Frank A. E. KRUYT ◽  
Giuseppe GIACCONE
Keyword(s):  
Subcellular Localization ◽  
Nuclear Export ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Nuclear Export Signal ◽  
Cowpox Virus ◽  
Amino Acid Region ◽  
Localization Signal ◽  
Induced Apoptosis ◽  
Export Signal

The cowpox virus-encoded anti-apoptotic protein cytokine response modifier A (CrmA) is a member of the serpin family that specifically inhibits the cellular proteins caspase 1, caspase 8 and granzyme B. In this study, we have used Flag- and yellow fluorescent protein (YFP)-tagged versions of CrmA to investigate the mechanisms that regulate its subcellular localization. We show that CrmA can actively enter and exit the nucleus and we demonstrate the role of the nuclear export receptor CRM1 in this shuttling process. CrmA contains a novel leucine-rich nuclear export signal (NES) that is functionally conserved in the anti-apoptotic cellular serpin PI-9. Besides this leucine-rich export signal, additional sequences mapping to a 103-amino-acid region flanking the NES contribute to the CRM1-dependent nuclear export of CrmA. Although YFP-tagged CrmA is primarily located in the cytoplasm, shifting its localization to be predominantly nuclear by fusion of a heterologous nuclear localization signal did not impair its ability to prevent Fas-induced apoptosis. We propose that nucleocytoplasmic shuttling would allow CrmA to efficiently target cellular pro-apoptotic proteins not only in the cytoplasm, but also in the nucleus, and thus to carry out its anti-apoptotic function in both compartments.

scholarly journals The Carboxy Terminus of Prospero Regulates Its Subcellular Localization

2003 ◽  
Vol 23 (3) ◽  
pp. 1014-1024 ◽  
Author(s):  
Xiaolin Bi ◽  
Andrey V. Kajava ◽  
Tamara Jones ◽  
Zoya N. Demidenko ◽  
Mark A. Mortin
Keyword(s):  
Subcellular Localization ◽  
Cell Fate ◽  
Nuclear Export ◽  
System Development ◽  
Nuclear Export Signal ◽  
Nervous System Development ◽  
Carboxy Terminus ◽  
Nuclear Exclusion ◽  
Multiple Processes ◽  
Embryonic Nervous System

ABSTRACT Subcellular localization of the transcription factor Prospero is dynamic. For example, the protein is cytoplasmic in neuroblasts, nuclear in sheath cells, and degraded in newly formed neurons. The carboxy terminus of Prospero, including the homeodomain and Prospero domain, plays roles in regulating these changes. The homeodomain has two distinct subdomains, which exclude proteins from the nucleus, while the intact homeo/Prospero domain masks this effect. One subdomain is an Exportin-dependent nuclear export signal requiring three conserved hydrophobic residues, which models onto helix 1. Another, including helices 2 and 3, requires proteasome activity to degrade nuclear protein. Finally, the Prospero domain is missing in prosI13 embryos, thus unmasking nuclear exclusion, resulting in constitutively cytoplasmic protein. Multiple processes direct Prospero regulation of cell fate in embryonic nervous system development.

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