scholarly journals Subcellular Localization Signals of bHLH-PAS Proteins: Their Significance, Current State of Knowledge and Future Perspectives

2019 ◽  
Vol 20 (19) ◽  
pp. 4746
Author(s):  
Beata Greb-Markiewicz ◽  
Marta Kolonko
Keyword(s):  
Transcription Factors ◽  
Nuclear Export ◽  
Protein Localization ◽  
Nuclear Localization Signals ◽  
Extracellular Signals ◽  
Helix Loop Helix ◽  
Current State ◽  
Activation Of Transcription ◽  
Living Organisms ◽  
Current Stage

The bHLH-PAS (basic helix-loop-helix/ Period-ARNT-Single minded) proteins are a family of transcriptional regulators commonly occurring in living organisms. bHLH-PAS members act as intracellular and extracellular “signals” sensors, initiating response to endo- and exogenous signals, including toxins, redox potential, and light. The activity of these proteins as transcription factors depends on nucleocytoplasmic shuttling: the signal received in the cytoplasm has to be transduced, via translocation, to the nucleus. It leads to the activation of transcription of particular genes and determines the cell response to different stimuli. In this review, we aim to present the current state of knowledge concerning signals that affect shuttling of bHLH-PAS transcription factors. We summarize experimentally verified and published nuclear localization signals/nuclear export signals (NLSs/NESs) in the context of performed in silico predictions. We have used most of the available NLS/NES predictors. Importantly, all our results confirm the existence of a complex system responsible for protein localization regulation that involves many localization signals, which activity has to be precisely controlled. We conclude that the current stage of knowledge in this area is still not complete and for most of bHLH-PAS proteins an experimental verification of the activity of further NLS/NES is needed.

scholarly journals Nuclear export of OLIG2 in neural stem cells is essential for ciliary neurotrophic factor–induced astrocyte differentiation

2004 ◽  
Vol 166 (7) ◽  
pp. 963-968 ◽  
Author(s):  
Takao Setoguchi ◽  
Toru Kondo
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Subventricular Zone ◽  
Nuclear Export ◽  
Ciliary Neurotrophic Factor ◽  
Extracellular Signals ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Astrocyte Differentiation ◽  
Oligodendrocyte Development

Neural stem cell (NSC) differentiation is precisely controlled by a network of transcription factors, which themselves are regulated by extracellular signals (Bertrand et al., 2002; Shirasakiand and Pfaff, 2002). One way that the activity of such transcription factors is controlled is by the regulation of their movement between the cytosol and nucleus (Vandromme et al., 1996. Lei and Silver, 2002). Here we show that the basic helix–loop–helix transcription factor OLIG2, which has been shown to be required for motor neuron and oligodendrocyte development, is found in the cytoplasm, but not the nucleus, of astrocytes in culture and of a subset of astrocytes in the subventricular zone. We demonstrate that the accumulation of OLIG2 in the nucleus of NSCs blocks the CNTF-induced astrocyte differentiation and that the translocation of OLIG2 to the cytoplasm is promoted by activated AKT. We propose that the AKT-stimulated export of OLIG2 from the nucleus of NSCs is essential for the astrocyte differentiation.

scholarly journals bHLH–PAS Proteins: Their Structure and Intrinsic Disorder

2019 ◽  
Vol 20 (15) ◽  
pp. 3653 ◽  
Author(s):  
Marta Kolonko ◽  
Beata Greb-Markiewicz
Keyword(s):  
X Ray ◽  
Intrinsically Disordered ◽  
Helix Loop Helix ◽  
Knowledge Based ◽  
Current State ◽  
Conserved Domain ◽  
Living Organisms ◽  
Nmr Methods ◽  
And Function

The basic helix–loop–helix/Per-ARNT-SIM (bHLH–PAS) proteins are a class of transcriptional regulators, commonly occurring in living organisms and highly conserved among vertebrates and invertebrates. These proteins exhibit a relatively well-conserved domain structure: the bHLH domain located at the N-terminus, followed by PAS-A and PAS-B domains. In contrast, their C-terminal fragments present significant variability in their primary structure and are unique for individual proteins. C-termini were shown to be responsible for the specific modulation of protein action. In this review, we present the current state of knowledge, based on NMR and X-ray analysis, concerning the structural properties of bHLH–PAS proteins. It is worth noting that all determined structures comprise only selected domains (bHLH and/or PAS). At the same time, substantial parts of proteins, comprising their long C-termini, have not been structurally characterized to date. Interestingly, these regions appear to be intrinsically disordered (IDRs) and are still a challenge to research. We aim to emphasize the significance of IDRs for the flexibility and function of bHLH–PAS proteins. Finally, we propose modern NMR methods for the structural characterization of the IDRs of bHLH–PAS proteins.

scholarly journals Importins and Exportins Regulating Allergic Immune Responses

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Ankita Aggarwal ◽  
Devendra K. Agrawal
Keyword(s):  
Transcription Factors ◽  
Nuclear Export ◽  
Molecular Mechanisms ◽  
Allergic Diseases ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Immune Modulators ◽  
Nuclear Localization Signals ◽  
Intracellular Signals ◽  
Pore Complexes

Nucleocytoplasmic shuttling of macromolecules is a well-controlled process involving importins and exportins. These karyopherins recognize and bind to receptor-mediated intracellular signals through specific signal sequences that are present on cargo proteins and transport into and out of the nucleus through nuclear pore complexes. Nuclear localization signals (NLS) present on cargo molecules to be imported while nuclear export signals (NES) on the molecules to be exported are recognized by importins and exportins, respectively. The classical NLS are found on many transcription factors and molecules that are involved in the pathogenesis of allergic diseases. In addition, several immune modulators, including corticosteroids and vitamin D, elicit their cellular responses by regulating the expression and activity of importin molecules. In this review article, we provide a comprehensive list of importin and exportin molecules and their specific cargo that shuttled between cytoplasm and the nucleus. We also critically review the role and regulation of specific importin and exportin involved in the transport of activated transcription factors in allergic diseases, the underlying molecular mechanisms, and the potential target sites for developing better therapeutic approaches.

scholarly journals CDK Phosphorylation of a Novel NLS-NES Module Distributed between Two Subunits of the Mcm2-7 Complex Prevents Chromosomal Rereplication

2005 ◽  
Vol 16 (10) ◽  
pp. 5026-5039 ◽  
Author(s):  
Muluye E. Liku ◽  
Van Q. Nguyen ◽  
Audrey W. Rosales ◽  
Kaoru Irie ◽  
Joachim J. Li
Keyword(s):  
Nuclear Localization ◽  
Nuclear Export ◽  
Protein Localization ◽  
Nuclear Export Signal ◽  
Replication Initiation ◽  
Nuclear Localization Signals ◽  
Cdk Phosphorylation ◽  
In Cis ◽  
Net Export ◽  
Cdk Regulation

Cyclin-dependent kinases (CDKs) use multiple mechanisms to block reassembly of prereplicative complexes (pre-RCs) at replication origins to prevent inappropriate rereplication. In Saccharomyces cerevisiae, one of these mechanisms promotes the net nuclear export of a pre-RC component, the Mcm2-7 complex, during S, G2, and M phases. Here we identify two partial nuclear localization signals (NLSs) on Mcm2 and Mcm3 that are each necessary, but not sufficient, for nuclear localization of the Mcm2-7 complex. When brought together in cis, however, the two partial signals constitute a potent NLS, sufficient for robust nuclear localization when fused to an otherwise cytoplasmic protein. We also identify a Crm1-dependent nuclear export signal (NES) adjacent to the Mcm3 NLS. Remarkably, the Mcm2-Mcm3 NLS and the Mcm3 NES are sufficient to form a transport module that recapitulates the cell cycle-regulated localization of the entire Mcm2-7 complex. Moreover, we show that CDK regulation promotes net export by phosphorylation of the Mcm3 portion of this module and that nuclear export of the Mcm2-7 complex is sufficient to disrupt replication initiation. We speculate that the distribution of partial transport signals among distinct subunits of a complex may enhance the specificity of protein localization and raises the possibility that previously undetected distributed transport signals are used by other multiprotein complexes.

From many to one: Meditation and the plasticity of the predictive mind

2020 ◽  
Author(s):  
Ruben Laukkonen ◽  
Heleen A Slagter
Keyword(s):  
Cognitive Enhancement ◽  
The Self ◽  
Predictive Processing ◽  
Focused Attention ◽  
Conceptual Processing ◽  
Current State ◽  
Contemplative Science ◽  
Open Monitoring ◽  
Living Organisms ◽  
The Brain

How profoundly can humans change their own minds? In this paper we offer a unifying account of meditation under the predictive processing view of living organisms. We start from relatively simple axioms. First, the brain is an organ that serves to predict based on past experience, both phylogenetic and ontogenetic. Second, meditation serves to bring one closer to the here and now by disengaging from anticipatory processes. We propose that practicing meditation therefore gradually reduces predictive processing, in particular counterfactual cognition—the tendency to construct abstract and temporally deep representations—until all conceptual processing falls away. Our Many- to-One account also places three main styles of meditation (focused attention, open monitoring, and non-dual meditation) on a single continuum, where each technique progressively relinquishes increasingly engrained habits of prediction, including the self. This deconstruction can also make the above processes available to introspection, permitting certain insights into one’s mind. Our review suggests that our framework is consistent with the current state of empirical and (neuro)phenomenological evidence in contemplative science, and is ultimately illuminating about the plasticity of the predictive mind. It also serves to highlight that contemplative science can fruitfully go beyond cognitive enhancement, attention, and emotion regulation, to its more traditional goal of removing past conditioning and creating conditions for potentially profound insights. Experimental rigor, neurophenomenology, and no-report paradigms combined with neuroimaging are needed to further our understanding of how different styles of meditation affect predictive processing and the self, and the plasticity of the predictive mind more generally.

Benzo[a]pyrene-dependent activation of transcription factors NF-κB and AP-1 related to tumor promotion in hepatoma cell cultures

2007 ◽  
Vol 72 (5) ◽  
pp. 552-557 ◽  
Author(s):  
N. A. Bolotina ◽  
A. V. Gasparian ◽  
T. K. Dubovaja ◽  
V. A. Evteev ◽  
V. A. Kobliakov
Keyword(s):  
Transcription Factors ◽  
Cell Cultures ◽  
Hepatoma Cell ◽  
Tumor Promotion ◽  
Activation Of Transcription
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