Intrinsically Disordered Domain of Kinesin-3 Kif14 Enables Unique Functional Diversity

Zhernov, Ilia; Diez, Stefan; Braun, Marcus; Lánský, Zdeněk

doi:10.1016/j.cub.2020.06.039

Cited by 18 publications

(12 citation statements)

References 89 publications

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“…The increase in processivity may also be due to the presence of a non-motor microtubule-binding site at the far C terminus of full-length CENP-E, as CENP-E 754 -2mNeon lacks this region [ 28 – 30 ]. Many kinesins have a second non-specific microtubule-binding site, which increases their residency time and processivity [ 31 – 33 ].…”

Section: Discussionmentioning

confidence: 99%

Reconstitution of an active human CENP-E motor

2022

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CENP-E is a large kinesin motor protein which plays pivotal roles in mitosis by facilitating chromosome capture and alignment, and promoting microtubule flux in the spindle. So far, it has not been possible to obtain active human CENP-E to study its molecular properties. Xenopus CENP-E motor has been characterized in vitro and is used as a model motor; however, its protein sequence differs significantly from human CENP-E. Here, we characterize human CENP-E motility in vitro . Full-length CENP-E exhibits an increase in run length and longer residency times on microtubules when compared to CENP-E motor truncations, indicating that the C-terminal microtubule-binding site enhances the processivity when the full-length motor is active. In contrast with constitutively active human CENP-E truncations, full-length human CENP-E has a reduced microtubule landing rate in vitro , suggesting that the non-motor coiled-coil regions self-regulate motor activity. Together, we demonstrate that human CENP-E is a processive motor, providing a useful tool to study the mechanistic basis for how human CENP-E drives chromosome congression and spindle organization during human cell division.

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Section: Discussionmentioning

confidence: 99%

Reconstitution of an active human CENP-E motor

2022

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“…Among the four genes of the GPS, KIF14, LATS2, and PRKCE have been widely studied in previous studies. For example, kinesin family member 14 (KIF14), a microtubule-dependent cytoskeletal motor protein, is involved in cytokinesis [ 45 ]. KIF14 overexpression is linked to several cancers, and KIF14 causes resistance to sorafenib and chemotherapy through the AKT signaling pathway in cancers [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a GPX4-Related Immune Prognostic Signature for Lung Adenocarcinoma

Feng

Chen

et al. 2022

Journal of Oncology

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Lung adenocarcinoma (LUAD) is a commonly occurring histological subtype of lung cancer. Glutathione peroxidase 4 (GPX4) is an important regulatory factor of ferroptosis and is involved in the development of many cancers, but its prognostic significance has not been systematically described in LUAD. In this study, we focused on developing a robust GPX4-related prognostic signature (GPS) for LUAD. Data for the training cohort was extracted from The Cancer Genome Atlas, and that for the validation cohort was sourced from the GSE72094 dataset including 863 LUAD patients. GPX4-related genes were screened out by weighted gene coexpression network analysis and Spearman’s correlation analysis. Then, Cox regression and least absolute shrinkage and selection operator regression analyses were employed to construct a GPS. The ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and GSEA were utilized to evaluate the relationship between GPS and the tumor microenvironment (TME). We constructed and validated a GPS premised on four GPX4-related genes (KIF14, LATS2, PRKCE, and TM6SF1), which could classify LUAD patients into low- and high-score cohorts. The high-risk cohort presented noticeably poorer overall survival (OS) as opposed to the low-risk cohort, meaning that the GPS may be utilized as an independent predictor of the OS of LUAD. The GPS was also adversely correlated with multiple tumor-infiltrating immune cells and immune-related processes and pathways in TME. Furthermore, greater sensitivity to erlotinib and lapatinib were identified in the low-risk cohort based on the GDSC database. Our findings suggest that the GPS can effectively forecast the prognosis of LUAD patients and may possibly regulate the TME of LUAD.

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“…The increase in processivity may also be due to the presence of a non-motor microtubule binding site at the far C terminus of full-length CENP-E, as CENP-E 754 lacks this region (Liao et al, 1994;Musinipally et al, 2013;Welburn, 2013). Many kinesins have a second non-specific microtubule binding site which increase their residency time and processivity (Mayr et al, 2011;McHugh et al, 2018;Zhernov et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Reconstitution of an active human CENP-E motor

Craske

Legal

Welburn

2022

Preprint

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CENP-E is a large kinesin motor protein which plays pivotal roles in mitosis by facilitating chromosome capture, alignment and promoting microtubule flux in the spindle. So far, it has not been possible to obtain active human CENP-E to study its molecular properties. Xenopus CENP-E motor has been characterised in vitro and is used as a model motor, however its protein sequence differs significantly from human CENP-E. Here, we characterise human CENP-E motility in vitro. Full-length CENP-E exhibits an increase in run length and longer residency times on microtubules when compared to CENP-E motor truncations, indicating that the C-terminal microtubule binding site enhances the processivity when the full-length motor is active. In contrast to constitutively active human CENP-E truncations, full-length human CENP-E has a reduced microtubule landing rate in vitro, suggesting that the non-motor coiled coil regions self-regulate motor activity. Together, we demonstrate that human CENP-E is a processive motor, providing a useful tool to study the mechanistic basis for how human CENP-E drives chromosome congression and spindle organisation during human cell division.

show abstract

Intrinsically Disordered Domain of Kinesin-3 Kif14 Enables Unique Functional Diversity

Cited by 18 publications

References 89 publications

Reconstitution of an active human CENP-E motor

Reconstitution of an active human CENP-E motor

Identification and Validation of a GPX4-Related Immune Prognostic Signature for Lung Adenocarcinoma

Reconstitution of an active human CENP-E motor

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