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Article ; Online: Antiviral Protein-Protein Interaction Inhibitors.

Marković, Violeta / Szczepańska, Anna / Berlicki, Łukasz

2024 Volume 67, Issue 5, Page(s) 3205–3231

Abstract: Continually repeating outbreaks of pathogenic viruses necessitate the construction of effective antiviral strategies. Therefore, the development of new specific antiviral drugs in a well-established and efficient manner is crucial. Taking into account ... ...

Abstract	Continually repeating outbreaks of pathogenic viruses necessitate the construction of effective antiviral strategies. Therefore, the development of new specific antiviral drugs in a well-established and efficient manner is crucial. Taking into account the strong ability of viruses to change, therapies with diversified molecular targets must be sought. In addition to the widely explored viral enzyme inhibitor approach, inhibition of protein-protein interactions is a very valuable strategy. In this Perspective, protein-protein interaction inhibitors targeting HIV, SARS-CoV-2, HCV, Ebola, Dengue, and Chikungunya viruses are reviewed and discussed. Antibodies, peptides/peptidomimetics, and small molecules constitute three classes of compounds that have been explored, and each of them has some advantages and disadvantages for drug development.
MeSH term(s)	Humans ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Viruses ; Enzyme Inhibitors ; Chikungunya virus ; Hemorrhagic Fever, Ebola/drug therapy
Chemical Substances	Antiviral Agents ; Enzyme Inhibitors
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.3c01543
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Article ; Online: Phosphatidylinositol 4-phosphate: a key determinant of plasma membrane identity and function in plants.

Marković, Vedrana / Jaillais, Yvon

The New phytologist

2022 Volume 235, Issue 3, Page(s) 867–874

Abstract: Phosphatidylinositol 4-phosphate (PI4P) is an anionic phospholipid which has been described as a master regulator of the Golgi apparatus in eukaryotic cells. However, recent evidence suggests that PI4P mainly accumulates at the plasma membrane in all ... ...

Abstract	Phosphatidylinositol 4-phosphate (PI4P) is an anionic phospholipid which has been described as a master regulator of the Golgi apparatus in eukaryotic cells. However, recent evidence suggests that PI4P mainly accumulates at the plasma membrane in all plant cells analyzed so far. In addition, many functions that are typically attributed to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P
MeSH term(s)	Animals ; Cell Membrane/metabolism ; Golgi Apparatus/metabolism ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Phosphatidylinositol Phosphates/metabolism ; Phosphatidylinositols/metabolism
Chemical Substances	Phosphatidylinositol 4,5-Diphosphate ; Phosphatidylinositol Phosphates ; Phosphatidylinositols ; phosphatidylinositol 4-phosphate
Language	English
Publishing date	2022-06-08
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	208885-x
ISSN	1469-8137 ; 0028-646X
ISSN (online)	1469-8137
ISSN	0028-646X
DOI	10.1111/nph.18258
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Article: Gait Characteristics during Dual-Task Walking in Elderly Subjects of Different Ages.

Nedović, Nenad / Eminović, Fadilj / Marković, Vladana / Stanković, Iva / Radovanović, Saša

Brain sciences

2024 Volume 14, Issue 2

Abstract: Background: In older age, walking ability gradually decreases due to factors including impaired balance, reduced muscle strength, and impaired vision and proprioception. Further, cognitive functions play a key role during walking and gradually decline ... ...

Abstract	Background: In older age, walking ability gradually decreases due to factors including impaired balance, reduced muscle strength, and impaired vision and proprioception. Further, cognitive functions play a key role during walking and gradually decline with age. There is greater variability in gait parameters when the demands during walking increase, in dual- and multiple-task situations. The aim of this study was to analyze gait parameters while performing a demanding cognitive and motor dual task in three different age-related healthy elderly subject groups. Method: A total of 132 healthy individuals (54 males, 78 females) were divided into three groups-55 to 65, 66 to 75, and 76 to 85 years. The subjects performed a basic walking task, dual motor task, dual mental task, and combined motor and mental task while walking. The gait parameters cycle time, stride length, swing time, and double support time were noted, as well as the variability of those parameters. Results: Cycle time was longer and stride length was shorter in the >76-year-old group than in the 51-65-year-old group in all test conditions. A comparison of all three groups did not show a significant difference in swing time, while double support time was increased in the same group. Conclusions: Changes are observed when gait is performed simultaneously with an additional motor or cognitive task. Early detection of gait disorders can help identify elderly people at increased risk of falls. Employing a dual-task paradigm during gait assessment in healthy elderly subjects may help identify cognitive impairment early in the course of the disturbance.
Language	English
Publishing date	2024-01-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci14020148
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Article: Phosphatidylinositol 4‐phosphate: a key determinant of plasma membrane identity and function in plants

Marković, Vedrana / Jaillais, Yvon

The new phytologist. 2022 Aug., v. 235, no. 3

2022

Abstract: Phosphatidylinositol 4‐phosphate (PI4P) is an anionic phospholipid which has been described as a master regulator of the Golgi apparatus in eukaryotic cells. However, recent evidence suggests that PI4P mainly accumulates at the plasma membrane in all ... ...

Abstract	Phosphatidylinositol 4‐phosphate (PI4P) is an anionic phospholipid which has been described as a master regulator of the Golgi apparatus in eukaryotic cells. However, recent evidence suggests that PI4P mainly accumulates at the plasma membrane in all plant cells analyzed so far. In addition, many functions that are typically attributed to phosphatidylinositol 4,5‐bisphosphate (PI(4,5)P₂) in animal and yeast cells are also supported by PI4P in plants. For example, PI4P is the key anionic lipid that powers the strong electrostatic properties of the plasma membrane. Phosphatidylinositol 4‐phosphate is also required for the establishment of stable membrane contacts between the endoplasmic reticulum and the plasma membrane, for exocytosis and to support signaling pathways. Thus, we propose that PI4P has a prominent role in specifying the identity of the plasma membrane and in supporting some of its key functions and should be considered a hallmark lipid of this compartment.
Keywords	Golgi apparatus ; animals ; endoplasmic reticulum ; exocytosis ; phospholipids ; plasma membrane ; yeasts
Language	English
Dates of publication	2022-08
Size	p. 867-874.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	208885-x
ISSN	1469-8137 ; 0028-646X
ISSN (online)	1469-8137
ISSN	0028-646X
DOI	10.1111/nph.18258
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The WAVE3/β-catenin oncogenic signaling regulates chemoresistance in triple negative breast cancer.

Wang, Wei / Rana, Priyanka S / Markovic, Vesna / Sossey-Alaoui, Khalid

Breast cancer research : BCR

2023 Volume 25, Issue 1, Page(s) 31

Abstract: Background: Metastatic breast cancer is responsible for the death of the majority of breast cancer patients. In fact, metastatic BC is the 2nd leading cause of cancer-related deaths in women in the USA and worldwide. Triple negative breast cancer (TNBC), ...

Abstract	Background: Metastatic breast cancer is responsible for the death of the majority of breast cancer patients. In fact, metastatic BC is the 2nd leading cause of cancer-related deaths in women in the USA and worldwide. Triple negative breast cancer (TNBC), which lacks expression of hormone receptors (ER-α and PR) and ErbB2/HER2, is especially lethal due to its highly metastatic behavior, propensity to recur rapidly, and for its resistance to standard of care therapies, through mechanisms that remain incompletely understood. WAVE3 has been established as a promoter of TNBC development and metastatic progression. In this study, we investigated the molecular mechanisms whereby WAVE3 promotes therapy-resistance and cancer stemness in TNBC, through the regulation of β-catenin stabilization. Methods: The Cancer Genome Atlas dataset was used to assess the expression of WAVE3 and β-catenin in breast cancer tumors. Kaplan-Meier Plotter analysis was used to correlate expression of WAVE3 and β-catenin with breast cancer patients' survival probability. MTT assay was used to quantify cell survival. CRISPR/Cas9-mediated gene editing, 2D and 3D tumorsphere growth and invasion assays, Immunofluorescence, Western blotting, Semi-quantitative and real-time quantitative PCR analyses were applied to study the WAVE3/β-catenin oncogenic signaling in TNBC. Tumor xenograft assays were used to study the role of WAVE3 in mediating chemotherapy resistance of TNBC tumors. Results: Genetic inactivation of WAVE3 in combination of chemotherapy resulted in inhibition of 2D growth and 3D tumorsphere formation and invasion of TNBC cells in vitro, as well as tumor growth and metastasis in vivo. In addition, while re-expression of phospho-active WAVE3 in the WAVE3-deficient TNBC cells restored the oncogenic activity of WAVE3, re-expression of phospho-mutant WAVE3 did not. Further studies revealed that dual blocking of WAVE3 expression or phosphorylation in combination with chemotherapy treatment inhibited the activity and expression and stabilization of β-catenin. Most importantly, the combination of WAVE3-deficiency or WAVE3-phospho-deficiency and chemotherapy suppressed the oncogenic behavior of chemoresistant TNBC cells, both in vitro and in vivo. Conclusion: We identified a novel WAVE3/β-catenin oncogenic signaling axis that modulates chemoresistance of TNBC. This study suggests that a targeted therapeutic strategy against WAVE3 could be effective for the treatment of chemoresistant TNBC tumors.
MeSH term(s)	Female ; Humans ; beta Catenin/genetics ; beta Catenin/metabolism ; beta Catenin/therapeutic use ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm/genetics ; Neoplasm Recurrence, Local ; Signal Transduction ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/pathology
Chemical Substances	beta Catenin ; WASF3 protein, human ; CTNNB1 protein, human
Language	English
Publishing date	2023-03-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-023-01634-3
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Article ; Online: Suicide Bombing Terrorism - CORRIGENDUM.

Tin, Derrick / Galehan, Jordan / Markovic, Vesna / Ciottone, Gregory R

Prehospital and disaster medicine

2022 Volume 37, Issue 1, Page(s) 145–146

MeSH term(s)	Bombs ; Explosions ; Humans ; Suicide ; Terrorism
Language	English
Publishing date	2022-01-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	1025975-2
ISSN	1945-1938 ; 1049-023X
ISSN (online)	1945-1938
ISSN	1049-023X
DOI	10.1017/S1049023X22000176
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Article ; Online: Functional Specialization within the EXO70 Gene Family in Arabidopsis.

Marković, Vedrana / Kulich, Ivan / Žárský, Viktor

International journal of molecular sciences

2021 Volume 22, Issue 14

Abstract: Localized delivery of plasma-membrane and cell-wall components is a crucial process for plant cell growth. One of the regulators of secretory-vesicle targeting is the exocyst tethering complex. The exocyst mediates first interaction between transport ... ...

Abstract	Localized delivery of plasma-membrane and cell-wall components is a crucial process for plant cell growth. One of the regulators of secretory-vesicle targeting is the exocyst tethering complex. The exocyst mediates first interaction between transport vesicles and the target membrane before their fusion is performed by SNARE proteins. In land plants, genes encoding the EXO70 exocyst subunit underwent an extreme proliferation with 23 paralogs present in the Arabidopsis (
MeSH term(s)	Arabidopsis/genetics ; Arabidopsis/growth & development ; Arabidopsis/metabolism ; Arabidopsis Proteins/genetics ; Arabidopsis Proteins/metabolism ; Cell Membrane/metabolism ; Exocytosis ; Gene Expression Regulation, Plant ; Transport Vesicles/metabolism ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/metabolism
Chemical Substances	Arabidopsis Proteins ; Vesicular Transport Proteins
Language	English
Publishing date	2021-07-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22147595
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Article ; Online: The WAVE2/miR-29/Integrin-β1 Oncogenic Signaling Axis Promotes Tumor Growth and Metastasis in Triple-negative Breast Cancer.

Rana, Priyanka S / Wang, Wei / Markovic, Vesna / Szpendyk, Justin / Chan, Ernest Ricky / Sossey-Alaoui, Khalid

Cancer research communications

2023 Volume 3, Issue 1, Page(s) 160–174

Abstract: Breast cancer is the most frequently diagnosed malignancy in women and the major cause of death because of its invasion, metastasis, and resistance to therapies capabilities. The most aggressive subtype of breast cancer is triple-negative breast cancer ( ... ...

Abstract	Breast cancer is the most frequently diagnosed malignancy in women and the major cause of death because of its invasion, metastasis, and resistance to therapies capabilities. The most aggressive subtype of breast cancer is triple-negative breast cancer (TNBC) due to invasive and metastatic properties along with early age of diagnosis and poor prognosis. TNBC tumors do not express estrogen, progesterone, and HER2 receptors, which limits their treatment with targeted therapies. Cancer invasiveness and metastasis are known to be promoted by increased cell motility and upregulation of the WAVE proteins. While the contribution of WAVE2 to cancer progression is well documented, the WAVE2-mediated regulation of TNBC oncogenic properties is still under investigated, as does the molecular mechanisms by which WAVE2 regulates such oncogenic pathways. In this study, we show that WAVE2 plays a significant role in TNBC development, progression, and metastasis, through the regulation of miR-29 expression, which in turn targets Integrin-β1 ( Significance: Identification of a novel WAVE2/miR-29/
MeSH term(s)	Humans ; Female ; Triple Negative Breast Neoplasms/genetics ; Integrin beta1/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; MicroRNAs/genetics
Chemical Substances	Integrin beta1 ; MicroRNAs
Language	English
Publishing date	2023-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2767-9764
ISSN (online)	2767-9764
DOI	10.1158/2767-9764.CRC-22-0249
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Article ; Online: Publisher Correction: Phosphorylation of the proline-rich domain of WAVE3 drives its oncogenic activity in breast cancer.

Kansakar, Urna / Wang, Wei / Markovic, Vesna / Sossey-Alaoui, Khalid

Scientific reports

2021 Volume 11, Issue 1, Page(s) 15800

Language	English
Publishing date	2021-07-29
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-94981-0
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Article ; Online: Phosphorylation of the proline-rich domain of WAVE3 drives its oncogenic activity in breast cancer.

Kansakar, Urna / Wang, Wei / Markovic, Vesna / Sossey-Alaoui, Khalid

Scientific reports

2021 Volume 11, Issue 1, Page(s) 3868

Abstract: Post-translational modification of proteins, such as tyrosine phosphorylation, plays a major role in driving the oncogenic activity of oncogenes. WAVE3 (WASF3), an adaptor and actin cytoskeleton remodeling protein, contributes to cell migration, cancer ... ...

Abstract	Post-translational modification of proteins, such as tyrosine phosphorylation, plays a major role in driving the oncogenic activity of oncogenes. WAVE3 (WASF3), an adaptor and actin cytoskeleton remodeling protein, contributes to cell migration, cancer cell invasion, and metastasis. WAVE3 plays a vital role in the progression and metastasis of triple negative breast cancer (TNBC), in part through the regulation of cancer stem cells (CSCs). Several studies have shown that WAVE3 tyrosine phosphorylation is required for its oncogenic activity. Moreover, our recent study showed that the proline rich domain (PRD) of WAVE3 is required for maintenance of the CSC niche in breast cancer by regulating the nuclear translocation of the CSC-specific nuclear transcription factor YB1. Here, we show that the PRD domain of WAVE3 and its phosphorylation are essential for driving the oncogenic activity of WAVE3. We show that phosphorylation of WAVE3 PRD is essential for migration and invasion of breast cancer cells in vitro, as well as tumor growth and metastasis in vivo. Mechanistically, we show that phosphorylation of the WAVE3 PRD is essential for interaction between WAVE3 and YB1. Loss of PRD phosphorylation inhibits such interaction and the YB1-mediated activation of expression of CSC markers, as well as the WAVE3 mediated activation of EMT. Together, our study identifies a novel role of WAVE3 and its PRD domain in the regulation of the invasion metastasis cascade in BC that is independent of the known function of WAVE3 as an actin cytoskeleton remodeling protein through the WAVE regulatory complex (WRC).
MeSH term(s)	Animals ; Carcinogenesis/metabolism ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Mice ; Phosphorylation ; Platelet-Derived Growth Factor/metabolism ; Proline-Rich Protein Domains ; Protein-Tyrosine Kinases/metabolism ; Stem Cell Niche ; Triple Negative Breast Neoplasms/metabolism ; Wiskott-Aldrich Syndrome Protein Family/metabolism ; Y-Box-Binding Protein 1/metabolism
Chemical Substances	Platelet-Derived Growth Factor ; WASF3 protein, human ; Wasf3 protein, mouse ; Wiskott-Aldrich Syndrome Protein Family ; Y-Box-Binding Protein 1 ; Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2021-02-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-83479-4
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