Discovering nuclear targeting signal sequence through protein language learning and multivariate analysis

Guo, Yun; Yang, Yang; Huang, Yan; Shen, Hong‐Bin

doi:10.1016/j.ab.2019.113565

Cited by 30 publications

(19 citation statements)

References 29 publications

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“…TH2 may contain weak or non‐conventional NLS beyond the detection of most predictors. Nonetheless, a web server predicted the KKKAD sequence, amino acids 384–388, as an NLS for TH2 (Guo et al., 2020; http://www.csbio.sjtu.edu.cn/bioinf/INSP/). The function of this predicted NLS in TH2 requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

THIAMIN REQUIRING2 is involved in thiamin diphosphate biosynthesis and homeostasis

et al. 2022

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SUMMARY The THIAMIN REQUIRING2 (TH2) protein comprising a mitochondrial targeting peptide followed by a transcription enhancement A and a haloacid dehalogenase domain is a thiamin monophosphate (TMP) phosphatase in the vitamin B1 biosynthetic pathway. The Arabidopsis th2‐3 T‐DNA insertion mutant was chlorotic and deficient in thiamin diphosphate (TDP). Complementation assays confirmed that haloacid dehalogenase domain alone was sufficient to rescue the th2‐3 mutant. In pTH2:TH2‐GFP/th2‐3 complemented plants, the TH2‐GFP was localized to the cytosol, mitochondrion, and nucleus, indicating that the vitamin B1 biosynthetic pathway extended across multi‐subcellular compartments. Engineered TH2‐GFP localized to the cytosol, mitochondrion, nucleus, and chloroplast, could complement the th2 mutant. Together, these results highlight the importance of intracellular TMP and thiamin trafficking in vitamin B1 biosynthesis. In an attempt to enhance the production of thiamin, we created various constructs to overexpress TH2‐GFP in the cytosol, mitochondrion, chloroplast, and nucleus. Unexpectedly, overexpressing TH2‐GFP resulted in an increase rather than a decrease in TMP. While studies on th2 mutants support TH2 as a TMP phosphatase, analyses of TH2‐GFP overexpression lines implicating TH2 may also function as a TDP phosphatase in planta. We propose a working model that the TMP/TDP phosphatase activity of TH2 connects TMP, thiamin, and TDP into a metabolic cycle. The TMP phosphatase activity of TH2 is required for TDP biosynthesis, and the TDP phosphatase activity of TH2 may modulate TDP homeostasis in Arabidopsis.

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Section: Discussionmentioning

confidence: 99%

THIAMIN REQUIRING2 is involved in thiamin diphosphate biosynthesis and homeostasis

et al. 2022

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“…Besides the 23 amino acids in the N-terminus of p85S6K which are predicted to be a NLS sequence, an additional NLS signal of 9 amino acids has also been found near the C-tail of p85S6K ( www.csbio.sjtu.edu.cn/bioinf/INSP/ , Additional file 1 : Fig. S12) [ 50 ]. This may explain why p70S6K can also be found to locate in nucleus.…”

Section: Discussionmentioning

confidence: 99%

p85S6K sustains synaptic GluA1 to ameliorate cognitive deficits in Alzheimer’s disease

Chen

et al. 2023

Transl Neurodegener

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Background Ribosomal protein S6 kinase 1 (S6K1) is a serine–threonine kinase that has two main isoforms: p70S6K (70-kDa isoform) and p85S6K (85-kDa isoform). p70S6K, with its upstream mammalian target of rapamycin (mTOR), has been shown to be involved in learning and memory and participate in the pathophysiology of Alzheimer’s disease (AD). However, the function of p85S6K has long been neglected due to its high similarity to p70S6k. The role of p85S6K in learning and memory is still largely unknown. Methods We fractionated the postsynaptic densities to illustrate the differential distribution of p85S6K and p70S6K. Coimmunoprecipitation was performed to unveil interactions between p85S6K and the GluA1 subunit of AMPA receptor. The roles of p85S6K in synaptic targeting of GluA1 and learning and memory were evaluated by specific knockdown or overexpression of p85S6K followed by a broad range of methodologies including immunofluorescence, Western blot, in situ proximity ligation assay, morphological staining and behavioral examination. Further, the expression level of p85S6K was measured in brains from AD patients and AD model mice. Results p85S6K, but not p70S6K, was enriched in the postsynaptic densities. Moreover, knockdown of p85S6K resulted in defective spatial and recognition memory. In addition, p85S6K could interact with the GluA1 subunit of AMPA receptor through synapse-associated protein 97 and A-kinase anchoring protein 79/150. Mechanistic studies demonstrated that p85S6K could directly phosphorylate GluA1 at Ser845 and increase the amount of GluA1 in synapses, thus sustaining synaptic function and spine densities. Moreover, p85S6K was found to be specifically decreased in the synaptosomal compartment in the brains of AD patients and AD mice. Overexpression of p85S6K ameliorated the synaptic deficits and cognitive impairment in transgenic AD model mice. Conclusions These results strongly imply a significant role for p85S6K in maintaining synaptic and cognitive function by interacting with GluA1. The findings provide an insight into the rational targeting of p85S6K as a therapeutic potential for AD.

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“…Plant-mPloc ( Chou and Shen, 2010 ) was used to predict the subcellular localization for amino acid sequences of the 11 GbPLATZ s. The sequence predicted with a nuclear localization was submitted to Identification of Nucleus Signal Peptide from Protein Primary Sequence (INSP; Guo et al, 2020 ) for nuclear localization signal recognition. To verify the prediction results, six GbPLATZ s expressed during ginkgo seed development were tested by protoplast subcellular localization.…”

Section: Methodsmentioning

confidence: 99%

“…was submitted to Identification of Nucleus Signal Peptide from Protein Primary Sequence (INSP; Guo et al, 2020) for nuclear localization signal recognition. To verify the prediction results, six GbPLATZs expressed during ginkgo seed development were tested by protoplast subcellular localization.…”

Section: Expression Profile Of Gbplatzsmentioning

confidence: 99%

Genome-Wide Identification of PLATZ Transcription Factors in Ginkgo biloba L. and Their Expression Characteristics During Seed Development

Han

Rong²,

Tian³

et al. 2022

Front. Plant Sci.

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Plant AT-rich protein and zinc-binding protein (PLATZ) is a class of plant-specific zinc-dependent DNA-binding protein that binds to A/T-rich DNA sequences. PLATZ plays an important role in seed development, water tolerance, and cell proliferation in early plant growth. In this study, 11 GbPLATZs were identified from the ginkgo genome with complete PLATZ-conserved domains, which represents a smaller number compared with angiosperms. Multi-species phylogenetic analysis showed that PLATZ genes were conserved in seed plants, and the 11 members were represented by four groups, among which groups I and II were closely related. Analysis of gene structures, sequence module characteristics, and expression patterns showed that GbPLATZs were similar within and differed between groups. RNA-seq and qRT-PCR results showed that GbPLATZs had distinct expression patterns. Most genes were associated with seed development, among which six genes were highly related. Subcellular localization experiments showed that six GbPLATZ proteins related to seed development were localized in the nucleus, suggesting that they might function as traditional transcription factors. This study provides a basis for understanding the structural differentiation, evolutionary characteristics, expression profile, and potential functions of PLATZ transcription factors in Ginkgo biloba.

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Discovering nuclear targeting signal sequence through protein language learning and multivariate analysis

Cited by 30 publications

References 29 publications

THIAMIN REQUIRING2 is involved in thiamin diphosphate biosynthesis and homeostasis

THIAMIN REQUIRING2 is involved in thiamin diphosphate biosynthesis and homeostasis

p85S6K sustains synaptic GluA1 to ameliorate cognitive deficits in Alzheimer’s disease

Genome-Wide Identification of PLATZ Transcription Factors in Ginkgo biloba L. and Their Expression Characteristics During Seed Development

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