scholarly journals Identification of a Common Subnuclear Localization Signal

2007 ◽  
Vol 18 (10) ◽  
pp. 3966-3977 ◽  
Author(s):  
Karim Mekhail ◽  
Luis Rivero-Lopez ◽  
Ahmad Al-Masri ◽  
Caroline Brandon ◽  
Mireille Khacho ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Nuclear Localization Signal ◽  
Dynamic Properties ◽  
Consensus Sequence ◽  
Molecular Networks ◽  
Subnuclear Localization ◽  
Transcription Regulator ◽  
High Affinity ◽  
Localization Signal ◽  
Membrane Bound

Proteins share peptidic sequences, such as a nuclear localization signal (NLS), which guide them to particular membrane-bound compartments. Similarities have also been observed within different classes of signals that target proteins to membrane-less subnuclear compartments. Common localization signals affect spatial and temporal subcellular organization and are thought to allow the coordinated response of different molecular networks to a given signaling cue. Here we identify a higher-order and predictive code, {[RR(I/L)X3r](n, n≥1)+[L(φ/N)(V/L)](n,n>1)}, that establishes high-affinity interactions between a group of proteins and the nucleolus in response to a specific signal. This position-independent code is referred to as a nucleolar detention signal regulated by H+ (NoDSH+) and the class of proteins includes the cIAP2 apoptotic regulator, VHL ubiquitylation factor, HSC70 heat shock protein and RNF8 transcription regulator. By identifying a common subnuclear targeting consensus sequence, our work reveals rules governing the dynamics of subnuclear organization and ascribes new modes of regulation to several proteins with diverse steady-state distributions and dynamic properties.

scholarly journals CRM1-mediated Recycling of Snurportin 1 to the Cytoplasm

1999 ◽  
Vol 145 (2) ◽  
pp. 255-264 ◽  
Author(s):  
Efrosyni Paraskeva ◽  
Elisa Izaurralde ◽  
F. Ralf Bischoff ◽  
Jochen Huber ◽  
Ulrike Kutay ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Nuclear Localization Signal ◽  
Nuclear Export ◽  
Activation Domain ◽  
Large Domain ◽  
High Affinity ◽  
Importin Α ◽  
Localization Signal ◽  
Major Mediator ◽  
Rev Protein

Importin β is a major mediator of import into the cell nucleus. Importin β binds cargo molecules either directly or via two types of adapter molecules, importin α, for import of proteins with a classical nuclear localization signal (NLS), or snurportin 1, for import of m3G-capped U snRNPs. Both adapters have an NH2-terminal importin β–binding domain for binding to, and import by, importin β, and both need to be returned to the cytoplasm after having delivered their cargoes to the nucleus. We have shown previously that CAS mediates export of importin α. Here we show that snurportin 1 is exported by CRM1, the receptor for leucine-rich nuclear export signals (NESs). However, the interaction of CRM1 with snurportin 1 differs from that with previously characterized NESs. First, CRM1 binds snurportin 1 50-fold stronger than the Rev protein and 5,000-fold stronger than the minimum Rev activation domain. Second, snurportin 1 interacts with CRM1 not through a short peptide but rather via a large domain that allows regulation of affinity. Strikingly, snurportin 1 has a low affinity for CRM1 when bound to its m3G-capped import substrate, and a high affinity when substrate-free. This mechanism appears crucial for productive import cycles as it can ensure that CRM1 only exports snurportin 1 that has already released its import substrate in the nucleus.

scholarly journals Structural Basis of High-Affinity Nuclear Localization Signal Interactions with Importin-α

Traffic ◽  
2012 ◽  
Vol 13 (4) ◽  
pp. 532-548 ◽  
Author(s):  
Mary Marfori ◽  
Thierry G. Lonhienne ◽  
Jade K. Forwood ◽  
Bostjan Kobe
Keyword(s):  
Nuclear Localization ◽  
Nuclear Localization Signal ◽  
Structural Basis ◽  
High Affinity ◽  
Importin Α ◽  
Localization Signal

scholarly journals Nuclear import of BCL11B is mediated by a classical nuclear localization signal and not the Krüppel-like zinc fingers

2021 ◽  
Author(s):  
Piotr Grabarczyk ◽  
Martin Delin ◽  
Dorota Rogińska ◽  
Lukas Schulig ◽  
Hannes Forkel ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Nuclear Localization Signal ◽  
Zinc Fingers ◽  
Consensus Sequence ◽  
Direct Interaction ◽  
Cellular Processes ◽  
Importin Alpha ◽  
Relative Conservation ◽  
Localization Signal ◽  
Pass Through

The Krüppel-like transcription factor BCL11B is characterized by wide tissue distribution and crucial functions in key developmental and cellular processes and various pathologies including cancer or HIV infection. Although basics of BCL11B activity and relevant interactions with other proteins were uncovered, how this exclusively nuclear protein localizes to its compartment remained unclear. Here, we demonstrate that unlike other KLFs, BCL11B does not require the C-terminal DNA-binding domain to pass through the nuclear envelope but encodes an independent, previously unidentified nuclear localization signal (NLS) which is located distantly from the zinc finger domains and fulfills the essential criteria of an autonomous NLS. First, it can redirect a heterologous cytoplasmic protein to the nucleus. Second, its mutations cause aberrant localization of the protein of origin. Finally, we provide experimental and in silico evidences of the direct interaction with importin alpha. The relative conservation of this motif allows formulating a consensus sequence (K/R)K-X13-14-KR+K++ which can be found in all BCL11B orthologues among vertebrates and in the closely related protein BCL11A.

scholarly journals Coordinate Nuclear Targeting of the FANCD2 and FANCI Proteins via a FANCD2 Nuclear Localization Signal

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e81387 ◽  
Author(s):  
Rebecca A. Boisvert ◽  
Meghan A. Rego ◽  
Paul A. Azzinaro ◽  
Maurizio Mauro ◽  
Niall G. Howlett
Keyword(s):  
Nuclear Localization ◽  
Nuclear Localization Signal ◽  
Nuclear Targeting ◽  
Localization Signal

scholarly journals SUMO-1 Modification and Its Role in Targeting the Ran GTPase-activating Protein, RanGAP1, to the Nuclear Pore Complex

1998 ◽  
Vol 140 (3) ◽  
pp. 499-509 ◽  
Author(s):  
Michael J. Matunis ◽  
Jian Wu ◽  
Günter Blobel
Keyword(s):  
Nuclear Localization ◽  
Nuclear Localization Signal ◽  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Gtpase Activating Protein ◽  
Terminal Domain ◽  
Localization Signal

RanGAP1 is the GTPase-activating protein for Ran, a small ras-like GTPase involved in regulating nucleocytoplasmic transport. In vertebrates, RanGAP1 is present in two forms: one that is cytoplasmic, and another that is concentrated at the cytoplasmic fibers of nuclear pore complexes (NPCs). The NPC-associated form of RanGAP1 is covalently modified by the small ubiquitin-like protein, SUMO-1, and we have recently proposed that SUMO-1 modification functions to target RanGAP1 to the NPC. Here, we identify the domain of RanGAP1 that specifies SUMO-1 modification and demonstrate that mutations in this domain that inhibit modification also inhibit targeting to the NPC. Targeting of a heterologous protein to the NPC depended on determinants specifying SUMO-1 modification and also on additional determinants in the COOH-terminal domain of RanGAP1. SUMO-1 modification and these additional determinants were found to specify interaction between the COOH-terminal domain of RanGAP1 and a region of the nucleoporin, Nup358, between Ran-binding domains three and four. Together, these findings indicate that SUMO-1 modification targets RanGAP1 to the NPC by exposing, or creating, a Nup358 binding site in the COOH-terminal domain of RanGAP1. Surprisingly, the COOH-terminal domain of RanGAP1 was also found to harbor a nuclear localization signal. This nuclear localization signal, and the presence of nine leucine-rich nuclear export signal motifs, suggests that RanGAP1 may shuttle between the nucleus and the cytoplasm.

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