Kinesin KIFC1 actively transports bare double-stranded DNA

Farina, Francesca; Pierobon, Paolo; Delevoye, Cédric; Monnet, Jordan; Dingli, Florent; Loew, Damarys; Quanz, Maria; Dutreix, Marie; Cappello, Giovanni

doi:10.1093/nar/gkt204

Cited by 34 publications

(37 citation statements)

References 60 publications

(52 reference statements)

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“…Interestingly, most KIF5B labeled dysferlin-containing vesicles did not show long-range processive movement and are limited to local movements in resting L6 myotubes. These findings are consistent with reports describing processive and non-processive movements of kinesin-bound cargoes (36,37). Possible explanations for the non-processive behavior of a subpopulation of kinesin-containing dysferlin vesicles are that KIF5B may be bound to dysferlin-containing vesicles without sufficiently activating kinesin motor activity or without actively engaging microtubules (36) or perhaps the clustering of vesicles limits their motility or anchors them to another subcellular structure.…”

Section: Dysferlin-containing Vesicles Move Along Microtubules Via Kisupporting

confidence: 91%

Membrane damage-induced vesicle–vesicle fusion of dysferlin-containing vesicles in muscle cells requires microtubules and kinesin

McDade

Michele

2013

Human Molecular Genetics

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Mutations in the dysferlin gene resulting in dysferlin-deficiency lead to limb-girdle muscular dystrophy 2B and Myoshi myopathy in humans. Dysferlin has been proposed as a critical regulator of vesicle-mediated membrane resealing in muscle fibers, and localizes to muscle fiber wounds following sarcolemma damage. Studies in fibroblasts and urchin eggs suggest that trafficking and fusion of intracellular vesicles with the plasma membrane during resealing requires the intracellular cytoskeleton. However, the contribution of dysferlin-containing vesicles to resealing in muscle and the role of the cytoskeleton in regulating dysferlin-containing vesicle biology is unclear. Here, we use live-cell imaging to examine the behavior of dysferlin-containing vesicles following cellular wounding in muscle cells and examine the role of microtubules and kinesin in dysferlin-containing vesicle behavior following wounding. Our data indicate that dysferlin-containing vesicles move along microtubules via the kinesin motor KIF5B in muscle cells. Membrane wounding induces dysferlin-containing vesicle-vesicle fusion and the formation of extremely large cytoplasmic vesicles, and this response depends on both microtubules and functional KIF5B. In non-muscle cell types, lysosomes are critical mediators of membrane resealing, and our data indicate that dysferlincontaining vesicles are capable of fusing with lysosomes following wounding which may contribute to formation of large wound sealing vesicles in muscle cells. Overall, our data provide mechanistic evidence that microtubulebased transport of dysferlin-containing vesicles may be critical for resealing, and highlight a critical role for dysferlin-containing vesicle-vesicle and vesicle-organelle fusion in response to wounding in muscle cells.

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Section: Dysferlin-containing Vesicles Move Along Microtubules Via Kisupporting

confidence: 91%

Membrane damage-induced vesicle–vesicle fusion of dysferlin-containing vesicles in muscle cells requires microtubules and kinesin

McDade

Michele

2013

Human Molecular Genetics

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“…In addition to its mitotic spindle-specific roles, several other roles of HSET requiring or independent of its motor activity have been suggested such as a role in processing early endocytic vesicles [35], rat spermatogenesis [36] and active transport of bare double-stranded DNA [37]. Although it is presently unclear whether HSET performs all these functions in cancer cells, these studies bring to light the possibility that HSET's involvement in tumor biology could be multifaceted.…”

Section: Discussionmentioning

confidence: 99%

HSET overexpression fuels tumor progression via centrosome clustering-independent mechanisms in breast cancer patients

et al. 2015

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Human breast tumors harbor supernumerary centrosomes in almost 80% of tumor cells. Although amplified centrosomes compromise cell viability via multipolar spindles resulting in death-inducing aneuploidy, cancer cells tend to cluster extra centrosomes during mitosis. As a result cancer cells display bipolar spindle phenotypes to maintain a tolerable level of aneuploidy, an edge to their survival. HSET/KifC1, a kinesin-like minus-end directed microtubule motor has recently found fame as a crucial centrosome clustering molecule. Here we show that HSET promotes tumor progression via mechanisms independent of centrosome clustering. We found that HSET is overexpressed in breast carcinomas wherein nuclear HSET accumulation correlated with histological grade and predicted poor progression-free and overall survival. In addition, deregulated HSET protein expression was associated with gene amplification and/or translocation. Our data provide compelling evidence that HSET overexpression is pro-proliferative, promotes clonogenic-survival and enhances cell-cycle kinetics through G2 and M-phases. Importantly, HSET co-immunoprecipitates with survivin, and its overexpression protects survivin from proteasome-mediated degradation, resulting in its increased steady-state levels. We provide the first evidence of centrosome clustering-independent activities of HSET that fuel tumor progression and firmly establish that HSET can serve both as a potential prognostic biomarker and as a valuable cancer-selective therapeutic target.

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“…Such as, KIFC1 is associated with the nuclear membrane and acrosome in round and elongating spermatids (15) and is required for chromosome congression and alignment during mitosis (16). Farina et al reported that depletion of KIFC1 significantly decreases double-stranded DNA transport, which might provide new insight for gene therapy and DNA-based therapy (17). The exchange of intracellular substances is the driving force for the survival of cells, even more so for cancer cells.…”

Section: Original Articlementioning

confidence: 99%

The overexpression of KIFC1 was associated with the proliferation and prognosis of non-small cell lung cancer

Liu¹,

Zhan²,

Zhou³

et al. 2016

J. Thorac. Dis.

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Background: The kinesin family member C1 (KIFC1, also known as HSET) is a kinesin superfamily protein (KIFs). Although KIFC1 acts as a crucial role in the development of several human cancers, the KIFC1 expression profile and functional remain unclear in non-small cell lung cancer (NSCLC). Methods:We collected the fresh NSCLC samples and paired normal lung tissue in patients with lung cancer operation, and detected KIFC1 expression using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting. To expand on previous smaller-scale studies, NSCLC tissue microarrays (TMA) were analyzed by IHC. Finally, cell lines were employed to further probe the potential mechanisms, Results:In this study, we described that KIFC1 was significantly upregulated in NSCLC tissues compared with the corresponding normal tissues. Moreover, KIFC1 overexpression was associated with the poor overall survival (OS) of NSCLC patients, and siRNA-mediated knockdown of KIFC1 significantly suppressed tumor cell proliferation in vitro. Further verification showed that inhibition of KIFC1 gene expression caused the upregulation of the cyclin-dependent kinases inhibitor p21 and downregulation of the cell cycle driver protein cdc2, which arrested cells in the G2-M phase.Conclusions: we report that increased KIFC1 expression may promote cell proliferation and identified it as a biomarker of unfavorable prognosis in NSCLC patients.Keywords: Kinesin family member C1 (KIFC1); non-small cell lung cancer (NSCLC); cyclin-dependent kinase inhibitor 1A (p21); cell division cycle protein 2 homolog (cdc2); prognostic

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Kinesin KIFC1 actively transports bare double-stranded DNA

Cited by 34 publications

References 60 publications

Membrane damage-induced vesicle–vesicle fusion of dysferlin-containing vesicles in muscle cells requires microtubules and kinesin

Membrane damage-induced vesicle–vesicle fusion of dysferlin-containing vesicles in muscle cells requires microtubules and kinesin

HSET overexpression fuels tumor progression via centrosome clustering-independent mechanisms in breast cancer patients

The overexpression of KIFC1 was associated with the proliferation and prognosis of non-small cell lung cancer

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