scholarly journals Evolution of molecular determinants for SUMO-activating enzyme subcellular localization in plants

2020 ◽  
Author(s):  
Abraham Más ◽  
Laura Castaño-Miquel ◽  
Lorenzo Carretero-Paulet ◽  
Núria Colomé ◽  
Francesc Canals ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Regulatory Mechanism ◽  
Large Subunit ◽  
Post Translational Modification ◽  
Nuclear Localization Signals ◽  
Sumo Conjugation ◽  
Phylogenetic Studies ◽  
Molecular Determinants ◽  
Evolutionary Role

AbstractPost-translational modification by Small Ubiquitin-related Modifier (SUMO) is an essential regulatory mechanism in eukaryotes. In the cell, SUMO conjugates are highly enriched in the nucleus and, consistently, SUMOylation machinery components are mainly nuclear. Nonetheless, cytosolic SUMO targets also exist and the mechanisms that facilitate SUMO conjugation in the cytosol are unknown. Here, we show that the nuclear localization of the Arabidopsis SUMO activating enzyme large subunit SAE2 is dependent on two nuclear localization signals, the canonical NLS1 and the non-canonical NLS2 identified and validated here. NLS2 is proteolytic processed from SAE2 during seed development, facilitating SAE2 enrichment in the cytosol. Results obtained using transgenic plants expressing different SAE2 proteoforms suggest that SAE2 cytosolic enrichment could constitute a rapid signal for growth arrest. Phylogenetic studies indicated that the Arabidopsis NLS1-NLS2 structural organization is conserved only in seed plants, providing a potential evolutionary role of cytosolic SUMOylation in seed appearance.

Functional analysis of the SUMOylation pathway in Drosophila

2008 ◽  
Vol 36 (5) ◽  
pp. 868-873 ◽  
Author(s):  
Ana Talamillo ◽  
Jonatan Sánchez ◽  
Rosa Barrio
Keyword(s):  
Functional Analysis ◽  
Fine Tuning ◽  
Model Systems ◽  
Post Translational Modification ◽  
Reversible Process ◽  
Cellular Processes ◽  
Tuning Mechanism ◽  
Sumo Conjugation

SUMOylation, a reversible process used as a ‘fine-tuning’ mechanism to regulate the role of multiple proteins, is conserved throughout evolution. This post-translational modification affects several cellular processes by the modulation of subcellular localization, activity or stability of a variety of substrates. A growing number of proteins have been identified as targets for SUMOylation, although, for many of them, the role of SUMO conjugation on their function is unknown. The use of model systems might facilitate the study of SUMOylation implications in vivo. In the present paper, we have compiled what is known about SUMOylation in Drosophila melanogaster, where the use of genetics provides new insights on SUMOylation's biological roles.

scholarly journals Phosphorylation adjacent to the nuclear localization signal of human dUTPase abolishes nuclear import: structural and mechanistic insights

2013 ◽  
Vol 69 (12) ◽  
pp. 2495-2505 ◽  
Author(s):  
Gergely Róna ◽  
Mary Marfori ◽  
Máté Borsos ◽  
Ildikó Scheer ◽  
Enikő Takács ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nuclear Localization ◽  
Nuclear Localization Signal ◽  
Nucleocytoplasmic Transport ◽  
Wild Type ◽  
Post Translational Modification ◽  
Nuclear Localization Signals ◽  
M Phase ◽  
Importin Α ◽  
Localization Signal

Phosphorylation adjacent to nuclear localization signals (NLSs) is involved in the regulation of nucleocytoplasmic transport. The nuclear isoform of human dUTPase, an enzyme that is essential for genomic integrity, has been shown to be phosphorylated on a serine residue (Ser11) in the vicinity of its nuclear localization signal; however, the effect of this phosphorylation is not yet known. To investigate this issue, an integrated set of structural, molecular and cell biological methods were employed. It is shown that NLS-adjacent phosphorylation of dUTPase occurs during the M phase of the cell cycle. Comparison of the cellular distribution of wild-type dUTPase with those of hyperphosphorylation- and hypophosphorylation-mimicking mutants suggests that phosphorylation at Ser11 leads to the exclusion of dUTPase from the nucleus. Isothermal titration microcalorimetry and additional independent biophysical techniques show that the interaction between dUTPase and importin-α, the karyopherin molecule responsible for `classical' NLS binding, is weakened significantly in the case of the S11E hyperphosphorylation-mimicking mutant. The structures of the importin-α–wild-type and the importin-α–hyperphosphorylation-mimicking dUTPase NLS complexes provide structural insights into the molecular details of this regulation. The data indicate that the post-translational modification of dUTPase during the cell cycle may modulate the nuclear availability of this enzyme.

SUMO: getting it on

2007 ◽  
Vol 35 (6) ◽  
pp. 1409-1413 ◽  
Author(s):  
J. Anckar ◽  
L. Sistonen
Keyword(s):  
Biological Processes ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Sumo Conjugation ◽  
Lysine Residues ◽  
Ubiquitin Conjugating Enzyme ◽  
Specificity Determinants ◽  
Conjugating Enzyme

Post-translational modification of cellular proteins by the SUMO (small ubiquitin-related modifier) is involved in numerous modes of regulation in widely different biological processes. In contrast with ubiquitination, SUMO conjugation is highly specific in terms of target lysine residues, but many aspects of substrate and lysine selection by the SUMO conjugating machinery are still poorly understood. SUMOylation events usually occur on the ΨKXE SUMO consensus motifs, which mediate binding to Ubc9 (ubiquitin-conjugating enzyme 9), the SUMO E2 conjugating enzyme. Although most, if not all, SUMO conjugations are catalysed by Ubc9, far from all ΨKXE tetrapeptides are modified, demonstrating a need for additional specificity determinants in SUMOylation. Recent results intimately link regulation of SUMOylation to other post-translational modifications, including phosphorylation and acetylation and reveal that certain lysine residues are marked for SUMOylation by negatively charged amino acid residues or phosphorylation events immediately downstream of the consensus site. In the present review, we explore the intriguing role of extended motifs in the regulation of SUMO conjugation.

Role of nuclear localization signals in the DNA delivery function of Chikungunya virus capsid protein

2021 ◽  
Vol 702 ◽  
pp. 108822
Author(s):  
Nitika Gaurav ◽  
Praveen Kumar Tripathi ◽  
Vivek Kumar ◽  
Archana Chugh ◽  
Monica Sundd ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Nuclear Localization ◽  
Chikungunya Virus ◽  
Dna Delivery ◽  
Virus Capsid ◽  
Nuclear Localization Signals ◽  
Virus Capsid Protein

scholarly journals Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 131
Author(s):  
Mar Álvarez ◽  
Enrique Sapena-Ventura ◽  
Joanna Luczkowiak ◽  
Samara Martín-Alonso ◽  
Luis Menéndez-Arias
Keyword(s):  
Dna Synthesis ◽  
Large Subunit ◽  
Rnase H ◽  
Reverse Transcriptases ◽  
Cleavage Specificity ◽  
Double Stranded Dna ◽  
Molecular Determinants ◽  
Rt Inhibitors ◽  
Viral Genomic Rna

HIV reverse transcriptases (RTs) convert viral genomic RNA into double-stranded DNA. During reverse transcription, polypurine tracts (PPTs) resilient to RNase H cleavage are used as primers for plus-strand DNA synthesis. Nonnucleoside RT inhibitors (NNRTIs) can interfere with the initiation of plus-strand DNA synthesis by enhancing PPT removal, while HIV RT connection subdomain mutations N348I and N348I/T369I mitigate this effect by altering RNase H cleavage specificity. Now, we demonstrate that among approved nonnucleoside RT inhibitors (NNRTIs), nevirapine and doravirine show the largest effects. The combination N348I/T369I in HIV-1BH10 RT has a dominant effect on the RNase H cleavage specificity at the PPT/U3 site. Biochemical studies showed that wild-type HIV-1 and HIV-2 RTs were able to process efficiently and accurately all tested HIV PPT sequences. However, the cleavage accuracy at the PPT/U3 junction shown by the HIV-2EHO RT was further improved after substituting the sequence YQEPFKNLKT of HIV-1BH10 RT (positions 342–351) for the equivalent residues of the HIV-2 enzyme (HQGDKILKV). Our results highlight the role of β-sheets 17 and 18 and their connecting loop (residues 342–350) in the connection subdomain of the large subunit, in determining the RNase H cleavage window of HIV RTs.

scholarly journals SUMOylation in Phytopathogen Interactions: Balancing Invasion and Resistance

2021 ◽  
Vol 9 ◽  
Author(s):  
Manisha Sharma ◽  
Diana Fuertes ◽  
Jordi Perez-Gil ◽  
L. Maria Lois
Keyword(s):  
Plant Defense ◽  
Plant Immunity ◽  
Defense Responses ◽  
Post Translational Modification ◽  
Crop Species ◽  
Biotic Stresses ◽  
Sumo Conjugation ◽  
Pathogen Effectors ◽  
Successful Infection

Plants are constantly confronted by a multitude of biotic stresses involving a myriad of pathogens. In crops, pathogen infections result in significant agronomical losses worldwide posing a threat to food security. In order to enter plant tissues and establish a successful infection, phytopathogens have to surpass several physical, and chemical defense barriers. In recent years, post-translational modification (PTM) mechanisms have emerged as key players in plant defense against pathogens. PTMs allow a highly dynamic and rapid response in front of external challenges, increasing the complexity and precision of cellular responses. In this review, we focus on the role of SUMO conjugation (SUMOylation) in plant immunity against fungi, bacteria, and viruses. In plants, SUMO regulates multiple biological processes, ranging from development to responses arising from environmental challenges. During pathogen attack, SUMO not only modulates the activity of plant defense components, but also serves as a target of pathogen effectors, highlighting its broad role in plant immunity. Here, we summarize known pathogenic strategies targeting plant SUMOylation and, the plant SUMO conjugates involved in host-pathogen interactions. We also provide a catalog of candidate SUMO conjugates according to their role in defense responses. Finally, we discuss the complex role of SUMO in plant defense, focusing on key biological and experimental aspects that contribute to some controversial conclusions, and the opportunities for improving agricultural productivity by engineering SUMOylation in crop species.

Regulation of protein transport to the nucleus: central role of phosphorylation

1996 ◽  
Vol 76 (3) ◽  
pp. 651-685 ◽  
Author(s):  
D. A. Jans ◽  
S. Hubner
Keyword(s):  
Nuclear Localization ◽  
Protein Transport ◽  
Protein Import ◽  
Nuclear Protein ◽  
Nuclear Transport ◽  
Simian Virus 40 ◽  
Nuclear Accumulation ◽  
Control Of Gene Expression ◽  
Nuclear Localization Signals

Nuclear protein transport is integral to eukaryotic cell processes such as differentiation, transformation, and the control of gene expression. Although the targeting role of nuclear localization signals (NLSs) has been known for some time, more recent results indicate that NLS-dependent nuclear protein import is precisely regulated. Phosphorylation appears to be the main mechanism controlling the nuclear transport of a number of proteins, including transcription factors such as NFkappaB, c-rel, dorsal, and SWI5 from yeast. Cytoplasmic retention factors, intra- and intermolecular NLS masking, and NLS masking by phosphorylation are some of the mechanisms by which phosphorylation specifically regulates nuclear transport. Even nuclear localization of the archetypal NLS-containing simian virus 40 large tumor antigen (T-ag) is regulated, namely by the "CcN motif," which comprises the T-ag NLS ("N") determining ultimate subcellular destination, a casein kinase II site ("C") 13 amino acids NH2-terminal to the NLS modulating the rate of nuclear import, and a cyclin-dependent kinase site ("c") adjacent to the NLS regulating the maximal level of nuclear accumulation. The CcN motif appears to be a special form of phosphorylation-regulated NLS (prNLS), where phosphorylation at site(s) close to the NLS specifically regulates NLS function. The regulation of nuclear transport through phosphorylation and prNLSs appears to be common in eukaryotic cells from yeast and plants to higher mammals.

scholarly journals Localization of BRCA1 and a splice variant identifies the nuclear localization signal.

1997 ◽  
Vol 17 (1) ◽  
pp. 444-452 ◽  
Author(s):  
S Thakur ◽  
H B Zhang ◽  
Y Peng ◽  
H Le ◽  
B Carroll ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Splice Variant ◽  
Expression Vectors ◽  
Nuclear Localization Signals ◽  
Functional Regions ◽  
Immunofluorescence Studies ◽  
Localization Signal ◽  
Exon 11 ◽  
Inherited Mutations

Inherited mutations in BRCA1 confer susceptibility to breast and ovarian neoplasms. However, the function of BRCA1 and the role of BRCA1 in noninherited cancer remain unknown. Characterization of alternately spliced forms of BRCA1 may identify functional regions; thus, we constructed expression vectors of BRCA1 and a splice variant lacking exon 11, designated BRCA1 delta 672-4095. Immunofluorescence studies indicate nuclear localization of BRCA1 but cytoplasmic localization of BRCA1 delta 672-4095. Two putative nuclear localization signals (designated NLS1 and NLS2) were identified in exon 11; immunofluorescence studies indicate that only NLS1 is required for nuclear localization. RNA analysis indicates the expression of multiple, tissue-specific forms of BRCA1 RNAs; protein analysis with multiple antibodies suggests that at least three BRCA1 isoforms are expressed, including those lacking exon 11. The results suggest that BRCA1 is a nuclear protein and raise the possibility that splicing is one form of regulation of BRCA1 function by alteration of the subcellular localization of expressed proteins.

The role of protein acetylation in regulating mitochondrial fusion and fission

2021 ◽  
Author(s):  
Golam M. Uddin ◽  
Rafa Abbas ◽  
Timothy E. Shutt
Keyword(s):  
Mitochondrial Function ◽  
Regulatory Mechanism ◽  
Mitochondrial Fusion ◽  
Dynamic Processes ◽  
Protein Acetylation ◽  
Post Translational Modification ◽  
Acetylation Status

The dynamic processes of mitochondrial fusion and fission determine the shape of mitochondria, which can range from individual fragments to a hyperfused network, and influence mitochondrial function. Changes in mitochondrial shape can occur rapidly, allowing mitochondria to adapt to specific cues and changing cellular demands. Here, we will review what is known about how key proteins required for mitochondrial fusion and fission are regulated by their acetylation status, with acetylation promoting fission and deacetylation enhancing fusion. In particular, we will examine the roles of NAD+ dependant sirtuin deacetylases, which mediate mitochondrial acetylation, and how this post-translational modification provides an exquisite regulatory mechanism to co-ordinate mitochondrial function with metabolic demands of the cell.

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