Using a comprehensive approach to investigate the interaction between Kinesin-5/Eg5 and the microtubule

Guo, Wenhan; Sun, Shengjie; Sanchez, Jason E.; Lopez-Hernandez, Alan E; Ale, Tolulope A.; Chen, Jiawei; Afrin, Tanjina; W, Qiu; Xie, Yixin; Li, Lin

doi:10.1016/j.csbj.2022.08.020

Cited by 8 publications

(15 citation statements)

References 61 publications

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“…Our results show that the α/β tubulin complex has the strongest electrostatic attractive interactions followed by the β/α tubulin complex, while β/β and α/α tubulin complexes have weak attractive and repulsive electrostatic interactions, respectively. The key forces between α and β tubulins are the hydrogen bonds on the interface of the two tubulins, which is consistent with our previous work [26]. While salt bridges play the most significant role in holding α/α or β/β tubulin complex.…”

Section: Discussionsupporting

confidence: 91%

“…Computational methods have been widely used to study the functions of biomolecules [25][26][27][28][29] including tubulins. Dr. Alberto Redaelli's group evaluated the elastic constants of an α-/β-tubulin monomer and the interaction force between the components by means of molecular dynamics simulations, and constructed a mechanical model of the tubulin dimer [30]; Joshi and Dima studied the microscopic origins of the mechanical response in microtubules by probing features of the energy landscape of the tubulin monomers and tubulin heterodimer with molecular simulations [31]; Marracino's group explored the response of tubulin to strong electric fields at the nanosecond level in molecular dynamics simulations [32]; Dr. Aristide Dogariu' lab reported accurate optical measurements of tubulin polarizability in aqueous suspensions [33]; Andriy Kovalenko et al studied the microtubule stability by using the three-dimensional molecular theory of solvation [34].…”

Section: Introductionmentioning

confidence: 99%

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A Comprehensive Study on the Electrostatic Properties of Tubulin-Tubulin Complexes in Microtubules

Guo

Ale

Sun

et al. 2023

Cells

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Microtubules are key players in several stages of the cell cycle and are also involved in the transportation of cellular organelles. Microtubules are polymerized by α/β tubulin dimers with a highly dynamic feature, especially at the plus ends of the microtubules. Therefore, understanding the interactions among tubulins is crucial for characterizing microtubule dynamics. Studying microtubule dynamics can help researchers make advances in the treatment of neurodegenerative diseases and cancer. In this study, we utilize a series of computational approaches to study the electrostatic interactions at the binding interfaces of tubulin monomers. Our study revealed that among all the four types of tubulin-tubulin binding modes, the electrostatic attractive interactions in the α/β tubulin binding are the strongest while the interactions of α/α tubulin binding in the longitudinal direction are the weakest. Our calculations explained that due to the electrostatic interactions, the tubulins always preferred to form α/β tubulin dimers. The interactions between two protofilaments are the weakest. Thus, the protofilaments are easily separated from each other. Furthermore, the important residues involved in the salt bridges at the binding interfaces of the tubulins are identified, which illustrates the details of the interactions in the microtubule. This study elucidates some mechanistic details of microtubule dynamics and also identifies important residues at the binding interfaces as potential drug targets for the inhibition of cancer cells.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

A Comprehensive Study on the Electrostatic Properties of Tubulin-Tubulin Complexes in Microtubules

Guo

Ale

Sun

et al. 2023

Cells

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“…Tubulin is a major component of eukaryotic cells plays a key role in dynamic aggregation and disaggregation through influencing cell replication and division [ 38 ].TUBA1C is reported to be a multifunctional cytoskeletal protein and a α-tubulin isoform involved in the progression of mitosis and cell division [ 39 ]. High TUBA1C expression has been shown to be closely related to a poor prognosis in in various cancers, For example, the downregulation of TUBA1C inhibited the proliferation and migration of LUAD[ 13 ],hepatoma[ 17 ],and glioma[ 40 ] cells through cell cycle arrest, In addition, TUBA1C upregulates YAP expression and promotes aerobic glycolysis to promote breast cancer cell proliferation[ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

TUBA1C: a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression

et al. 2023

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Background The lack of obvious symptoms of early gastric cancer (GC) as well as the absence of sensitive and specific biomarkers results in poor clinical outcomes. Tubulin is currently emerging as important regulators of the microtubule cytoskeleton and thus have a strong potential to be implicated in a number of disorders, however, its mechanism of action in gastric cancer is still unclear. Tubulin alpha-1 C (TUBA1C) is a subtype of α-tubulin, high TUBA1C expression has been shown to be closely related to a poor prognosis in various cancers, this study, for the first time, revealed the mechanism of TUBA1C promotes malignant progression of gastric cancer in vitro and in vivo. Methods The expression of lncRNA EGFR-AS1 was detected in human GC cell lines by qRT–PCR. Mass spectrometry experiments following RNA pulldown assays found that EGFR-AS1 directly binds to TUBA1C, the CCK8, EdU, transwell, wound-healing, cell cycle assays and animal experiments were conducted to investigate the function of TUBA1C in GC. Combined with bioinformatics analyses, reveal interaction between Ki-67, E2F1, PCNA and TUBA1C by western blot. Rescue experiments furtherly demonstrated the relationship of EGFR-AS1and TUBA1C. Results TUBA1C was proved to be a direct target of EGFR-AS1, and TUBA1C promotes gastric cancer proliferation, migration and invasion by accelerating the progression of the cell cycle from the G1 phase to the S phase and activating the expression of oncogenes: Ki-67, E2F1 and PCNA. Conclusion TUBA1C is a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression and could be a novel biomarker and therapeutic target for GC.

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“…Tubulin is a major component of eukaryotic cells plays a key role in dynamic aggregation and disaggregation through in uencing cell replication and division [31].TUBA1C is reported to be a multifunctional cytoskeletal protein and a α-tubulin isoform involved in the progression of mitosis and cell division [32]. High TUBA1C expression has been shown to be closely related to a poor prognosis in in various cancers, For example, the downregulation of TUBA1C inhibited the proliferation and migration of hepatoma [11], PDAC [10],LUAD [7]and glioma [33] cells through cell cycle arrest, in addition, TUBA1C upregulates YAP expression and promotes aerobic glycolysis to promote breast cancer cell proliferation [8].…”

Section: Discussionmentioning

confidence: 99%

TUBA1C: a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression

Wang

Cui

Yang

et al. 2022

Preprint

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Background: The lack of obvious symptoms of early GC as well as the absence of sensitive and specific biomarkers results in poor clinical outcomes. High TUBA1C expression has been shown to be closely related to a poor prognosis in in various cancers, however, the role of TUBA1C in GC have not yet been elucidated. This study, for the first time, revealed that TUBA1C drives the growth of GC cell lines both in vitro and in vivo. Methods: The expression of lncRNA EGFR-AS1 was detected in human GC cell lines by qRT–PCR. MS experiments following RNA pulldown assays found that EGFR-AS1 directly binds to TUBA1C, the CCK8, EdU, transwell, wound-healing, cell cycle assays and animal experiments were conducted to investigate the function of TUBA1C in GC. Combined with bioinformatics analyses, reveal interaction between E2F1, Ki-67, PCNA and TUBA1C by western blot. Rescue experiments furtherly demonstrated the relationship of EGFR-AS1and TUBA1C. Results: TUBA1C was proved to be a direct target of EGFR-AS1, TUBA1C promotes gastric cancer proliferation, migration and invasion by accelerating the progression of the cell cycle from the G1 phase to the S phase and activating the expression of tumor suppressor genes: E2F1, Ki-67, and PCNA. Conclusions: TUBA1C is a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression and could be a novel biomarker and therapeutic target for GC.

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Using a comprehensive approach to investigate the interaction between Kinesin-5/Eg5 and the microtubule

Cited by 8 publications

References 61 publications

A Comprehensive Study on the Electrostatic Properties of Tubulin-Tubulin Complexes in Microtubules

A Comprehensive Study on the Electrostatic Properties of Tubulin-Tubulin Complexes in Microtubules

TUBA1C: a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression

TUBA1C: a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression

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