scholarly journals N-myristoyltransferase: Tracing Steps Backwards to Find a Way Forward

2020 ◽  
Author(s):  
Dean Reddick ◽  
Daniel I Udenwobele ◽  
David Datzkiw ◽  
Revanti Mukherjee ◽  
Shailly Varma Shrivastav ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nuclear Localization ◽  
Potential Role ◽  
Nuclear Localization Sequence ◽  
Amino Acid Residues ◽  
Trace Back ◽  
Carbon Fatty Acid ◽  
Localization Sequence ◽  
History Of ◽  
First Time

AbstractN-myristoylation refers to the attachment of a 14-carbon fatty acid onto the N-terminal glycine residue of a target protein. The myristoylation reaction, catalyzed by N-myristoyltrasnferase (NMT), is essential for regulating cellular activities such as signal transduction, proliferation, migration, differentiation, and transformation. Although a considerable amount of research is performed on the overexpression of NMT in pathogenic conditions, a fundamental knowledge gap exists on the evolution of NMT and the functional impact of myristoylation for normal cellular development and functions. We performed evolutionary analyses of the NMT gene and found that most non-vertebrates harbor a single nmt gene and all vertebrates examined harbor two genes; nmt1 and nmt2. For the first time, we report that teleosts harbor two copies of nmt1, named nmt1a and nmt1b. We traced the evolutionary history of the chromosomal fragments hosting NMT1 and NMT2 in humans and found that NMT1 and NMT2 trace back to a single vertebrate ancestral chromosome. We also report the presence of putative nuclear localization sequence (NLS) and amino acid residues flanking NLS. The presence of phosphorylatable amino acid residues flanking the NLS suggests that nuclear localization of NMT is regulated by phosphorylation. The nuclear localization of NMT suggest its potential role in gene transcription.

Elongator's toxin-target (TOT) function is nuclear localization sequence dependent and suppressed by post-translational modification

2003 ◽  
Vol 49 (5) ◽  
pp. 1297-1307 ◽  
Author(s):  
Lars Fichtner ◽  
Daniel Jablonowski ◽  
Angelika Schierhorn ◽  
Hiroko K. Kitamoto ◽  
Michael J. R. Stark ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Nuclear Localization Sequence ◽  
Post Translational Modification ◽  
Sequence Dependent ◽  
Localization Sequence

Novel properties of the protein kinase CK2-site-regulated nuclear- localization sequence of the interferon-induced nuclear factor IFI 16

2000 ◽  
Vol 353 (1) ◽  
pp. 69-77 ◽  
Author(s):  
Lyndall J. BRIGGS ◽  
Ricky W. JOHNSTONE ◽  
Rachel M. ELLIOT ◽  
Chong-Yun XIAO ◽  
Michelle DAWSON ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Nuclear Localization ◽  
Nuclear Import ◽  
Protein Kinase Ck2 ◽  
Protein Import ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Nuclear Localization Sequence ◽  
Localization Sequence ◽  
Kinase Ck2

Members of the interferon-induced class of nuclear factors possess a putative CcN motif, comparable with that within proteins such as the simian virus 40 large tumour antigen (T-ag), which confers phosphorylation-mediated regulation of nuclear-localization sequence (NLS)-dependent nuclear import. Here we examine the functionality of the interferon-induced factor 16 (IFI 16) CcN motif, demonstrating its ability to target a heterologous protein to the nucleus, and to be phosphorylated specifically by the CcN-motif-phosphorylating protein kinase CK2 (CK2). The IFI 16 NLS, however, has novel properties, conferring ATP-dependent nuclear import completely independent of cytosolic factors, as well as binding to nuclear components. The IFI 16 NLS is not recognized with high affinity by the NLS-binding importin heterodimer, and transport mediated by it is insensitive to non-hydrolysable GTP analogues. The IFI 16 NLS thus mediates nuclear import through a pathway completely distinct from that of conventional NLSs, such as that of T-ag, but intriguingly resembling that of the NLS of the HIV-1 transactivator protein Tat. Since the IFI 16 CK2 site enhances nuclear import through facilitating binding to nuclear components, this represents a novel mechanism by which the site regulates nuclear-protein import, and constitutes a difference between the IFI 16 and Tat NLSs that may be of importance in the immune response.

Hairless is translocated to the nucleus via a novel bipartite nuclear localization signal and is associated with the nuclear matrix

2001 ◽  
Vol 114 (2) ◽  
pp. 367-376
Author(s):  
K. Djabali ◽  
V.M. Aita ◽  
A.M. Christiano
Keyword(s):  
Amino Acid ◽  
Hair Follicle ◽  
Nuclear Localization ◽  
Nuclear Matrix ◽  
Nuclear Localization Signal ◽  
Amino Acid Residues ◽  
Bipartite Nuclear Localization Signal ◽  
Hairless Gene ◽  
Fractionation Analysis ◽  
Localization Signal

Hair follicle cycling is an exquisitely regulated and dynamic process consisting of phases of growth, regression and quiescence. The transitions between the phases are governed by a growing number of regulatory proteins, including transcription factors. The hairless (hr) gene encodes a putative transcription factor that is highly expressed in the skin, where it appears to be an essential regulator during the regression of the catagen hair follicle. In hairless mice, as well as humans with congenital atrichia, the absence of hr gene function initiates a premature and abnormal catagen due to a dysregulation of apoptosis and cell adhesion, and defects in the signaling required for hair follicle remodeling. Here, we report structure-function studies of the hairless gene product, in which we identify a novel bipartite nuclear localization signal (NLS) of the form KRA(X13) PKR. Deletion analysis of the mouse hr gene mapped the NLS to amino acid residues 409–427. Indirect immunofluorescence microscopy of cells transiently transfected with hairless-green fluorescent fusion proteins demonstrated that these amino acid residues are necessary and sufficient for nuclear localization. Furthermore, nuclear fractionation analysis revealed that the hr protein is associated with components of the nuclear matrix.

NLS (Nuclear Localization Sequence)

2012 ◽  
pp. 1245-1245
Author(s):  
Rüdiger Horstkorte ◽  
Bettina Büttner ◽  
Kaya Bork ◽  
Navdeep Sahota ◽  
Sarah Sabir ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Nuclear Localization Sequence ◽  
Localization Sequence

scholarly journals IPSE, a Parasite-Derived, Host Immunomodulatory Infiltrin Protein, Alleviates Resiniferatoxin-Induced Bladder Pain

2020 ◽  
Author(s):  
Kenji Ishida ◽  
Evaristus C. Mbanefo ◽  
Loc Le ◽  
Olivia Lamanna ◽  
Luke F. Pennington ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Analgesic Effect ◽  
Transient Receptor Potential ◽  
Nuclear Localization Sequence ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Bladder Pain ◽  
Nociceptive Neurons ◽  
Sequence Dependent ◽  
Localization Sequence

AbstractThe transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor is an important mediator of nociception and its expression is enriched in nociceptive neurons. TRPV1 signaling has been implicated in bladder pain and is a potential analgesic target. Resiniferatoxin is the most potent known agonist of TRPV1. Acute exposure of the rat bladder to resiniferatoxin has been demonstrated to result in pain-related freezing and licking behaviors that are alleviated by virally encoded IL-4. The interleukin-4-inducing principle of Schistosoma mansoni eggs (IPSE) is a powerful inducer of IL-4 secretion, and is also known to alter host cell transcription through a nuclear localization sequence-dependent mechanism. We previously reported that IPSE ameliorates ifosfamide-induced bladder pain in an IL-4- and nuclear localization sequence-dependent manner. We hypothesized that pre-administration of IPSE to resiniferatoxin-challenged mice would dampen pain-related behaviors. IPSE indeed lessened resiniferatoxin-triggered freezing behaviors in mice. This was a nuclear localization sequence-dependent phenomenon, since administration of a nuclear localization sequence mutant version of IPSE abrogated IPSE’s analgesic effect. In contrast, IPSE’s analgesic effect did not seem IL-4-dependent, since use of anti-IL-4 antibody in mice given both IPSE and resiniferatoxin did not dramatically affect freezing behaviors. RNA-Seq analysis of resiniferatoxin- and IPSE-exposed bladders revealed differential expression of TNF/NF-κb-related signaling pathway genes. In vitro testing of IPSE uptake by urothelial cells and TRPV1-expressing neuronal cells showed uptake by both cell types. Thus, IPSE’s nuclear localization sequence-dependent therapeutic effects on TRPV1-mediated bladder pain may act on TRPV1-expressing neurons and/or may rely upon urothelial mechanisms.

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