Structural analysis of human SEPHS2 protein, a selenocysteine machinery component, over-expressed in triple negative breast cancer Article Swipe
Carmine A. Nunziata
,
Andrea Polo
,
Angela Sorice
,
Francesca Capone
,
Marina Accardo
,
Eliana Guerriero
,
Federica Zito Marino
,
Michele Orditura
,
Alfredo Budillon
,
Susan Costantini
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-019-52718-0
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-019-52718-0
Selenophosphate synthetase 2 (SEPHS2) synthesizes selenide and ATP into selenophosphate, the selenium donor for selenocysteine (Sec), which is cotranslationally incorporated into selenoproteins. The action and regulatory mechanisms of SEPHS2 as well as its role in carcinogenesis (especially breast cancer) remain ambiguous and need further clarification. Therefore, lacking an experimentally determined structure for SEPHS2, we first analyzed the physicochemical properties of its sequence, modeled its three-dimensional structure and studied its conformational behavior to identify the key residues (named HUB nodes) responsible for protein stability and to clarify the molecular mechanisms by which it induced its function. Bioinformatics analysis evidenced higher amplification frequencies of SEPHS2 in breast cancer than in other cancer types. Therefore, because triple negative breast cancer (TNBC) is biologically the most aggressive breast cancer subtype and its treatment represents a challenge due to the absence of well-defined molecular targets, we evaluated SEPHS2 expression in two TNBC cell lines and patient samples. We demonstrated mRNA and protein overexpression to be correlated with aggressiveness and malignant tumor grade, suggesting that this protein could potentially be considered a prognostic marker and/or therapeutic target for TNBC.
Related Topics
Concepts
Triple-negative breast cancer
Breast cancer
Carcinogenesis
Cancer research
Cancer
Biology
Computational biology
Selenocysteine
Function (biology)
Mechanism (biology)
Chemistry
Cell biology
Genetics
Biochemistry
Enzyme
Cysteine
Philosophy
Epistemology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41598-019-52718-0
- https://www.nature.com/articles/s41598-019-52718-0.pdf
- OA Status
- gold
- Cited By
- 45
- References
- 45
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2983058656
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2983058656Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41598-019-52718-0Digital Object Identifier
- Title
-
Structural analysis of human SEPHS2 protein, a selenocysteine machinery component, over-expressed in triple negative breast cancerWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-11-06Full publication date if available
- Authors
-
Carmine A. Nunziata, Andrea Polo, Angela Sorice, Francesca Capone, Marina Accardo, Eliana Guerriero, Federica Zito Marino, Michele Orditura, Alfredo Budillon, Susan CostantiniList of authors in order
- Landing page
-
https://doi.org/10.1038/s41598-019-52718-0Publisher landing page
- PDF URL
-
https://www.nature.com/articles/s41598-019-52718-0.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.nature.com/articles/s41598-019-52718-0.pdfDirect OA link when available
- Concepts
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Triple-negative breast cancer, Breast cancer, Carcinogenesis, Cancer research, Cancer, Biology, Computational biology, Selenocysteine, Function (biology), Mechanism (biology), Chemistry, Cell biology, Genetics, Biochemistry, Enzyme, Cysteine, Philosophy, EpistemologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
45Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 4, 2024: 9, 2023: 17, 2022: 7, 2021: 6Per-year citation counts (last 5 years)
- References (count)
-
45Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.represents | 130 |
| abstract_inverted_index.suggesting | 168 |
| abstract_inverted_index.synthetase | 2 |
| abstract_inverted_index.(especially | 37 |
| abstract_inverted_index.frequencies | 101 |
| abstract_inverted_index.potentially | 173 |
| abstract_inverted_index.responsible | 80 |
| abstract_inverted_index.synthesizes | 5 |
| abstract_inverted_index.therapeutic | 180 |
| abstract_inverted_index.biologically | 120 |
| abstract_inverted_index.demonstrated | 154 |
| abstract_inverted_index.incorporated | 20 |
| abstract_inverted_index.well-defined | 138 |
| abstract_inverted_index.amplification | 100 |
| abstract_inverted_index.Bioinformatics | 96 |
| abstract_inverted_index.aggressiveness | 163 |
| abstract_inverted_index.carcinogenesis | 36 |
| abstract_inverted_index.clarification. | 45 |
| abstract_inverted_index.conformational | 70 |
| abstract_inverted_index.experimentally | 49 |
| abstract_inverted_index.overexpression | 158 |
| abstract_inverted_index.selenocysteine | 15 |
| abstract_inverted_index.Selenophosphate | 1 |
| abstract_inverted_index.physicochemical | 58 |
| abstract_inverted_index.selenoproteins. | 22 |
| abstract_inverted_index.selenophosphate, | 10 |
| abstract_inverted_index.cotranslationally | 19 |
| abstract_inverted_index.three-dimensional | 65 |
| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 89 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 10 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8199999928474426 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.85168356 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |