Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning

McHugh, Toni; Głuszek, A. Agata; Welburn, Julie

doi:10.1083/jcb.201705209

Cited by 62 publications

(88 citation statements)

References 44 publications

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“…As a kinesin family motor protein and microtubule‐binding protein, KIF18B plays a critical role in the regulation of microtubule (MT) dynamics and spindle positioning (McHugh et al, ; Tanenbaum et al, ). Previous studies confirmed the important role of KIF18B in the regulation of astral microtubule organization and mitosis (Lee et al, ; Walczak, Zong, Jain, & Stout, ).…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, targeting therapy has become a promising treatment for PDAC (Schmohl et al, ). Some drugs targeting common therapeutic targets for PDAC, such as epidermal growth factor receptor (EGFR), receptor tyrosine kinases, mammalian target of rapamycin, and vascular endothelial growth factor (VEGF), have some, but not obvious effects (McHugh, Gluszek, & Welburn, ; Stout et al, ). Therefore, novel therapeutic targets for PDAC are still urgently needed.…”

Section: Introductionmentioning

confidence: 99%

“…KIF18B was initially identified as a member of the kinesin family (Itzel et al, ). As a plus end‐directed motor protein, KIF18B moves along microtubules and controls MT end accumulation through EB1 (McHugh et al, ; Stout et al, ). Additionally, KIF18B is involved in the separation of chromosomes in mitosis and organizing astral MTs (Kim, Fonseca, & Stumpff, ).…”

Section: Introductionmentioning

confidence: 99%

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KIF18B promotes the proliferation of pancreatic ductal adenocarcinoma via activating the expression of CDCA8

Liu

Zhang

et al. 2019

Journal Cellular Physiology

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Pancreatic cancer is one of the malignant tumors with the worst prognosis, and the 5-year survival rate of this disease is less than 1%. About 90% of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), and targeting therapy has become a promising treatment for PDAC in recent years. To improve the survival rate, novel therapeutic targets for PDAC are still urgently needed. KIF18B was initially identified as a member of the kinesin family and involved in multiple cellular processes, such as separation of chromosomes in mitosis. Recently, it was found that KIF18B was involved in the growth and development of multiple cancers. However, the potential link between KIF18B and PDAC is still unclear. In this study, we demonstrated that KIF18B was highly expressed in human PDAC tissues, and related with the poor prognosis and clinical features, such as tumor size (*p = .013) and pTNM stage (*p = .025), of patients with PDAC. We further found that KIF18B knockdown blocked the cell proliferation of PDAC in vitro and in vivo, and the cell cycle was arrested caused by KIF18B depletion. Additionally, we also found that KIF18B bound to the promoter region of the cell division cycle associated 8 and thus activated its transcription. Taken together, this study explored the molecular mechanism underlying KIF18B promoting PDAC and provided a novel therapeutic target of this disease. K E Y W O R D SCDCA8, KIF18B, pancreatic ductal adenocarcinoma, proliferation, therapeutic target

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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KIF18B promotes the proliferation of pancreatic ductal adenocarcinoma via activating the expression of CDCA8

Liu

Zhang

et al. 2019

Journal Cellular Physiology

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“…They can walk on microtubules, but also regulate microtubule length, during mitosis (Gergely, Crapo, Hough, McIntosh, & Betterton, 2016;Grissom et al, 2009;Gupta, Carvalho, Roof, & Pellman, 2006;McHugh, Gluszek, & Welburn, 2018;Savoian & Glover, 2010), and/or ciliary and flagellar assembly (Hu, Liang, Meng, Wang, & Pan, 2015;Niwa et al, 2012;Wang et al, 2016). They can walk on microtubules, but also regulate microtubule length, during mitosis (Gergely, Crapo, Hough, McIntosh, & Betterton, 2016;Grissom et al, 2009;Gupta, Carvalho, Roof, & Pellman, 2006;McHugh, Gluszek, & Welburn, 2018;Savoian & Glover, 2010), and/or ciliary and flagellar assembly (Hu, Liang, Meng, Wang, & Pan, 2015;Niwa et al, 2012;Wang et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…While most kinesins display predominantly one activity, either transport along microtubules or depolymerization, kinesin-8 family members are reportedly multitalented. They can walk on microtubules, but also regulate microtubule length, during mitosis (Gergely, Crapo, Hough, McIntosh, & Betterton, 2016;Grissom et al, 2009;Gupta, Carvalho, Roof, & Pellman, 2006;McHugh, Gluszek, & Welburn, 2018;Savoian & Glover, 2010), and/or ciliary and flagellar assembly (Hu, Liang, Meng, Wang, & Pan, 2015;Niwa et al, 2012;Wang et al, 2016). In Plasmodium, PbKIN8B could therefore be involved in several steps of microgametogenesis, such as DNA replication, axoneme assembly and function, as well as male gamete exflagellation.…”

Section: Introductionmentioning

confidence: 99%

Vital role forPlasmodium bergheiKinesin8B in axoneme assembly during male gamete formation and mosquito transmission

Depoix

Marques

Ferguson

et al. 2019

Cellular Microbiology

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Sexual development is an essential phase in the Plasmodium life cycle, where male gametogenesis is an unusual and extraordinarily rapid process. It produces 8 haploid motile microgametes, from a microgametocyte within 15 minutes. Its unique achievement lies in linking the assembly of 8 axonemes in the cytoplasm to the three rounds of intranuclear genome replication, forming motile microgametes, which are expelled in a process called exflagellation. Surprisingly little is known about the actors involved in these processes. We are interested in kinesins, molecular motors that could play potential roles in male gametogenesis. We have undertaken a functional characterization in Plasmodium berghei of kinesin-8B (PbKIN8B) expressed specifically in male gametocytes and gametes. By generating Pbkin8B-gfp parasites, we show that PbKIN8B is specifically expressed during male gametogenesis and is associated with the axoneme. We created a ΔPbkin8B knockout cell line and analysed the consequences of the absence of PbKIN8B on male gametogenesis. We show that the ability to produce sexually differentiated gametocytes is not affected in ΔPbkin8B parasites and that the 3 rounds of genome replication occur normally. Nevertheless, the development to free motile microgametes is halted and the life cycle is interrupted in vivo. Ultrastructural analysis revealed that intranuclear mitoses are unaffected whereas cytoplasmic microtubules, although assembled in doublets and elongated, fail to assemble in the normal axonemal '9+2' structure and become motile. Absence of a functional axoneme prevented microgamete assembly and release from the microgametocyte, severely reducing infection of the mosquito vector. This is the first functional study of a kinesin involved in male gametogenesis.These results reveal a previously unknown role for PbKIN8B in male gametogenesis, providing new insights into Plasmodium flagellar formation.

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Silencing of KIF18B restricts proliferation and invasion and enhances the chemosensitivity of breast cancer via modulating Akt/GSK‐3β/β‐catenin pathway

Jiang

Liu

et al. 2021

BioFactors

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Kinesin family member 18B (KIF18B) is a new tumor-associated protein that contributes to the carcinogenesis of multiple malignancies. However, the detailed relevance of KIF18B in breast cancer has not been fully elucidated.This work aimed was to evaluate a possible relationship between KIF18B and breast cancer progression. Our findings show KIF18B is increased in breast cancer and demonstrate that high KIF18B level predicts a reduced survival rate. Cellular functional studies revealed that knockdown of KIF18B markedly reduces the proliferation, invasion, and epithelial-mesenchymal transition of breast cancer cells and enhances their chemosensitivity toward doxorubicin. Further studies showed that KIF18B modulates the level of phospho-Akt, phospho-glycogen synthase kinase-3β, and β-catenin. Notably, suppression of Akt abolished KIF18B-overexpression-induced increases in activation of Wnt/β-catenin pathway. In addition, re-expression of β-catenin reversed KIF18B-silencing-induced cancer-promoting effect. In vivo animal experiments elucidated that knockdown of KIF18B significantly weakened the tumorigenicity of breast cancer cells. Taken together, data of this study illustrate that KIF18B exerts a potential cancer-promoting function in breast cancer via enhancement of Wnt/β-catenin pathway through modulation of the Akt/GSK-3β axis.

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Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning

Abstract: Kinesin-8 Kif18b shortens astral microtubules in mitosis. Combining cell biology and biochemical reconstitution, McHugh et al. show that Kif18b walks and accumulates to microtubule plus ends in a phosphospecific manner to regulate astral microtubule dynamics and center the mitotic spindle.

Cited by 62 publications

References 44 publications

KIF18B promotes the proliferation of pancreatic ductal adenocarcinoma via activating the expression of CDCA8

KIF18B promotes the proliferation of pancreatic ductal adenocarcinoma via activating the expression of CDCA8

Vital role forPlasmodium bergheiKinesin8B in axoneme assembly during male gamete formation and mosquito transmission

Silencing of KIF18B restricts proliferation and invasion and enhances the chemosensitivity of breast cancer via modulating Akt/GSK‐3β/β‐catenin pathway

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