Computational identification of post-translational modification-based nuclear import regulations by characterizing nuclear localization signal-import receptor interaction

Lin, Jhih Rong; Liu, Zhonghao; Hu, Jianjun

doi:10.1002/prot.24642

Cited by 5 publications

(3 citation statements)

References 78 publications

(110 reference statements)

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“…NLS signals tend to be conserved between proteins, and are thus sensitive to alterations [13] . Our previous study has shown that phosphorylation on NLS residues has a dramatic impact on the binding ability of nuclear proteins to nuclear import receptors, and therefore affects nuclear localization efficiency [8] .…”

Section: Resultsmentioning

confidence: 99%

“…Post-transcriptional modification (PTM)-based modulation of the NLS binding affinity to import receptors is one of the most understood mechanisms that regulates the nuclear import of proteins [4][5][6][7] . Our previous study has developed an effective algorithm to predict nuclear import activity, in which molecular interaction energy components (MIECs) were used to characterize NLS-import receptor interaction, and a support vector regression machine(SVR) was used to learn the relationship between the characterized NLS-import receptor interaction and the corresponding nuclear import activity [8] . Based on our model, we developed a systematic framework to precisely predict how potential PTM, such as phosphorylation, regulates nuclear import of human and yeast nuclear proteins.…”

Section: Introductionmentioning

confidence: 99%

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Computational Identification of Phosphorylation Sites around Nuclear Localization Signal Sequence Reveals New Insight into Genes Associated With Human Diseases

Hu¹,

Internationals²

2017

JBPR

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Alterations in protein Subcellular localization often contribute to the development of human diseases. Post-transcriptional modifications, such as phosphorylation on the Nuclear Localization Signal (NLS), may change the protein's localization. However, little is known about the frequency and local effects of phosphorylation near NLS sites. In this study, a computer program was developed to search various databases in order to find proteins with NLS Phosphorylations, and any diseases that are associated with those genes. 308 NLS sequences were found in the NLSdb database, resulting in the identification of 133,448 NLS-containing proteins in the Uniprot database. We cross-referenced these proteins with phosphorylation data available from the PhosphoSitePlus database and found that about 21% of these NLS-containing proteins have evidence of phosphorylation sites. After plugging this into the gene disease association database, 138 of disease-associated genes (1% of NLS-containing proteins)were identified to have phosphorylation sites on their NLS sequences. Further evaluation of the NLS phosphorylation status of these genes in clinical samples may lead to development of new biomarkers for human diseases, and shed new light into the pathogenesis of these gene-associated diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Computational Identification of Phosphorylation Sites around Nuclear Localization Signal Sequence Reveals New Insight into Genes Associated With Human Diseases

Hu¹,

Internationals²

2017

JBPR

Self Cite

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“…NLS is a polybasic sequence comprised of multiple lysines (K) or arginines (R). Lin et al (2014) showed that template PxxK [KR] x [KR]xx (a very common NLS motif) may have many modifications and depended on binding affinity to its import receptor, and it can potentially have different nuclear import activity. Exon 1 of Rheb1 presents in both wild-type Rheb1 and mutant Rheb1/β-gal gene of our experimental mice.…”

Section: Discussionmentioning

confidence: 99%

RHEB1 expression in embryonic and postnatal mouse

Tian

Smart

Clement

et al. 2015

Histochem Cell Biol

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Ras homolog enriched in brain (RHEB1) is a member within the superfamily of GTP-binding proteins encoded by the RAS oncogenes. RHEB1 is located at the crossroad of several important pathways including the insulin-signaling pathways and thus plays an important role in different physiological processes. To understand better the physiological relevance of RHEB1 protein, the expression pattern of RHEB1 was analyzed in both embryonic (at E3.5-E16.5) and adult (1-month old) mice. RHEB1 immunostaining and X-gal staining were used for wild-type and Rheb1 gene trap mutant mice, respectively. These independent methods revealed similar RHEB1 expression patterns during both embryonic and postnatal developments. Ubiquitous uniform RHEB1/β-gal and/or RHEB1 expression was seen in preimplantation embryos at E3.5 and postimplantation embryos up to E12.5. Between stages E13.5 and E16.5, RHEB1 expression levels became complex: In particular, strong expression was identified in neural tissues, including the neuroepithelial layer of the mesencephalon, telencephalon, and neural tube of CNS and dorsal root ganglia. In addition, strong expression was seen in certain peripheral tissues including heart, intestine, muscle, and urinary bladder. Postnatal mice have broad spatial RHEB1 expression in different regions of the cerebral cortex, subcortical regions (including hippocampus), olfactory bulb, medulla oblongata, and cerebellum (particularly in Purkinje cells). Significant RHEB1 expression was also viewed in internal organs including the heart, intestine, urinary bladder, and muscle. Moreover, adult animals have complex tissue- and organ-specific RHEB1 expression patterns with different intensities observed throughout postnatal development. Its expression level is in general comparable in CNS and other organs of mouse. Thus, the expression pattern of RHEB1 suggests that it likely plays a ubiquitous role in the development of the early embryo with more tissue-specific roles in later development.

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Peptide-based non-viral gene delivery: A comprehensive review of the advances and challenges

Xiang,

Li,

Cong

et al. 2024

International Journal of Biological Macromolecules

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Computational identification of post-translational modification-based nuclear import regulations by characterizing nuclear localization signal-import receptor interaction

Cited by 5 publications

References 78 publications

Computational Identification of Phosphorylation Sites around Nuclear Localization Signal Sequence Reveals New Insight into Genes Associated With Human Diseases

Computational Identification of Phosphorylation Sites around Nuclear Localization Signal Sequence Reveals New Insight into Genes Associated With Human Diseases

RHEB1 expression in embryonic and postnatal mouse

Peptide-based non-viral gene delivery: A comprehensive review of the advances and challenges

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