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Kinesin

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https://www.readbyqxmd.com/read/28534180/the-c-terminal-kinesin-motor-kifc1-may-participate-in-nuclear-reshaping-and-flagellum-formation-during-spermiogenesis-of-larimichthys-crocea
#1
Dan-Dan Zhang, Xin-Ming Gao, Yong-Qiang Zhao, Cong-Cong Hou, Jun-Quan Zhu
Spermatogenesis is a highly ordered process in the differentiation of male germ cells. Nuclear morphogenesis is one of the most fundamental cellular transformations to take place during spermatogenesis. These striking transformations from spermatogonia to spermatozoa are a result of phase-specific adaption of the cytoskeleton and its association with molecular motor proteins. KIFC1 is a C-terminal kinesin motor protein that plays an essential role in acrosome formation and nuclear reshaping during spermiogenesis in mammals...
May 23, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28533507/kif4a-mediate-the-accumulation-and-reeducation-of-thp-1-derived-macrophages-via-regulation-of-ccl2-ccr2-expression-in-crosstalking-with-oscc
#2
Yun Zhang, Shaohua Liu, Daiwei Qu, Ketao Wang, Lin Zhang, Xuanxuan Jing, Chen Li, Fengcai Wei, Xun Qu
Crosstalk between tumor infiltrating macrophages and tumor cells is thought to play an indispensable role in oral squamous cell carcinomas (OSCC) by induction and maintenance of tolerance microenvironment. High infiltration of M2 macrophages and increasing expression of Kinesin family member 4A (Kif4A) in primary OSCC have been proved to correlate with greater tumoral size and poor clinical outcome. However, linkage between Kif4A and infiltrating macrophages in tumorigenesis and progression remains unclear...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533284/nesprin-1%C3%AE-2-is-essential-for-mouse-postnatal-viability-and-nuclear-positioning-in-skeletal-muscle
#3
Matthew J Stroud, Wei Feng, Jianlin Zhang, Jennifer Veevers, Xi Fang, Larry Gerace, Ju Chen
The position of the nucleus in a cell is controlled by interactions between the linker of nucleoskeleton and cytoskeleton (LINC) complex and the cytoskeleton. Defects in nuclear positioning and abnormal aggregation of nuclei occur in many muscle diseases and correlate with muscle dysfunction. Nesprin 1, which includes multiple isoforms, is an integral component of the LINC complex, critical for nuclear positioning and anchorage in skeletal muscle, and is thought to provide an essential link between nuclei and actin...
May 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28527407/mechanisms-of-resistance-to-systemic-therapy-in-metastatic-castration-resistant-prostate-cancer
#4
REVIEW
Giuseppe Galletti, Benjamin I Leach, Linda Lam, Scott T Tagawa
Patients with metastatic castration-resistant prostate cancer (mCPRC) now have an unprecedented number of approved treatment options, including chemotherapies (docetaxel, cabazitaxel), androgen receptor (AR)-targeted therapies (enzalutamide, abiraterone), a radioisotope (radium-223) and a cancer vaccine (sipuleucel-T). However, the optimal treatment sequencing pathway is unknown, and this problem is exacerbated by the issues of primary and acquired resistance. This review focuses on mechanisms of resistance to AR-targeted therapies and taxane-based chemotherapy...
May 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28525372/overexpression-of-a-novel-candidate-oncogene-kif14-correlates-with-tumor-progression-and-poor-prognosis-in-prostate-cancer
#5
Yixiang Zhang, Yeqing Yuan, Pei Liang, Zhaoxia Zhang, Xiaojing Guo, Ligang Xia, Yingying Zhao, Xing-Sheng Shu, Shengkun Sun, Ying Ying, Yingduan Cheng
Prostate cancer (PCa) is the second leading cause of death from cancer in men. The mechanism underlying tumorigenesis and development of PCa is largely unknown. Here, we identified Kinesin family member 14 (KIF14) as a novel candidate oncogene in PCa. We found that KIF14 was overexpressed in multiple PCa cell lines and primary PCa tissues. Knockdown of KIF14 in DU145 and PC3 prostate cancer cells suppressed cell proliferation, induced cell cycle arrest and apoptosis. Transcriptome analysis by RNA-sequencing demonstrated that KIF4 suppression led to transcriptional changes of genes involved in p53 and TGF-beta signaling pathway...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514735/kif7-attenuates-prostate-tumor-growth-through-lkb1-mediated-akt-inhibition
#6
Kai Yau Wong, Jing Liu, Kwok Wah Chan
This study investigated kinesin family member 7 (KIF7) expression and function in prostate cancer (PCa). Our results showed that KIF7 was significantly downregulated in PCa, compared with normal, benign prostatic hyperplasia and prostate intraepithelial neoplasia tissues, partially through promoter hypermethylation. We further investigated the effects of KIF7 coiled coil (CC) domain and motor domain (MD) on PCa development in vitro and in vivo. Our results showed that KIF7-CC but not KIF7-MD significantly attenuated proliferation and colony formation, impeded migration and invasion, induced apoptosis and sensitized PCa cells to paclitaxel...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28513584/kinesin-5-independent-mitotic-spindle-assembly-requires-the-antiparallel-microtubule-crosslinker-ase1-in-fission-yeast
#7
Sergio A Rincon, Adam Lamson, Robert Blackwell, Viktoriya Syrovatkina, Vincent Fraisier, Anne Paoletti, Meredith D Betterton, Phong T Tran
Bipolar spindle assembly requires a balance of forces where kinesin-5 produces outward pushing forces to antagonize the inward pulling forces from kinesin-14 or dynein. Accordingly, Kinesin-5 inactivation results in force imbalance leading to monopolar spindle and chromosome segregation failure. In fission yeast, force balance is restored when both kinesin-5 Cut7 and kinesin-14 Pkl1 are deleted, restoring spindle bipolarity. Here we show that the cut7Δpkl1Δ spindle is fully competent for chromosome segregation independently of motor activity, except for kinesin-6 Klp9, which is required for anaphase spindle elongation...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28505371/the-arm-domain-of-armadillo-repeat-kinesin-1-is-not-required-for-microtubule-catastrophe-but-can-negatively-regulate-nima-related-kinase-6-in-arabidopsis-thaliana
#8
Ryan C Eng, Laryssa S Halat, Samuel J Livingston, Tatsuya Sakai, Hiroyasu Motose, Geoffrey Wasteneys
Microtubules are dynamic filaments, the assembly and disassembly of which are under precise control of various associated proteins, including motor proteins and regulatory enzymes. In Arabidopsis thaliana, two such proteins are the ARMADILLO-REPEAT KINESIN 1 (ARK1), which promotes microtubule disassembly, and the NIMA-RELATED KINASE 6 (NEK6), which has a role in organizing microtubule arrays. Previous yeast 2-hybrid and in vitro pull-down assays determined that NEK6 can interact with ARK1 through the latter protein's Armadillo-repeat (ARM) cargo domain...
May 13, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28505193/the-drosophila-orthologue-of-the-int6-onco-protein-regulates-mitotic-microtubule-growth-and-kinetochore-structure
#9
Fioranna Renda, Claudia Pellacani, Anton Strunov, Elisabetta Bucciarelli, Valeria Naim, Giuseppe Bosso, Elena Kiseleva, Silvia Bonaccorsi, David J Sharp, Alexey Khodjakov, Maurizio Gatti, Maria Patrizia Somma
INT6/eIF3e is a highly conserved component of the translation initiation complex that interacts with both the 26S proteasome and the COP9 signalosome, two complexes implicated in ubiquitin-mediated protein degradation. The INT6 gene was originally identified as the insertion site of the mouse mammary tumor virus (MMTV), and later shown to be involved in human tumorigenesis. Here we show that depletion of the Drosophila orthologue of INT6 (Int6) results in short mitotic spindles and deformed centromeres and kinetochores with low intra-kinetochore distance...
May 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28504687/the-kinesin-kif14-is-overexpressed-in-medulloblastoma-and-downregulation-of-kif14-suppressed-tumor-proliferation-and-induced-apoptosis
#10
Kay Ka-Wai Li, Yan Qi, Tian Xia, Aden Ka-Yin Chan, Zhen-Yu Zhang, Abudumijiti Aibaidula, Rong Zhang, Liangfu Zhou, Yu Yao, Ho-Keung Ng
Medulloblastoma (MB) is the most common malignant brain tumor in childhood. At present, there is no well-established targeted drug for majority of patients. The kinesin family member 14 (KIF14) is a novel oncogene located on chromosome 1q and is dysregulated in multiple cancers. The objectives of this study were to evaluate KIF14 expression and chromosome 1q copy number in MB, and to delineate its biological functions in MB pathogenesis. By quantitative RT-PCR and immunohistochemistry, we found KIF14 was overexpressed in MB...
May 15, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28504639/structural-basis-of-cooperativity-in-kinesin-revealed-by-3d-reconstruction-of-a-two-head-bound-state-on-microtubules
#11
Daifei Liu, Xueqi Liu, Zhiguo Shang, Charles Vaughn Sindelar
The detailed basis of walking by dimeric molecules of kinesin along microtubules has remained unclear, partly because available structural methods have been unable to capture microtubule-bound intermediates of this process. Utilizing novel electron cryomicroscopy methods, we solved structures of microtubule-attached, dimeric kinesin bound to an ATP analog. We find that under these conditions, the kinesin dimer can attach to the microtubule with either one or two motor domains, and we present sub-nanometer resolution reconstructions of both states...
May 15, 2017: ELife
https://www.readbyqxmd.com/read/28496990/mtorc1-regulates-mannose-6-phosphate-receptor-transport-and-t-cell-vulnerability-to-regulatory-t-cells-by-controlling-kinesin-kif13a
#12
Khawaja Ashfaque Ahmed, Jim Xiang
Mannose-6-phosphate receptor (M6PR) that facilitates cellular uptake of M6P-bearing proteins, including serine-protease granzyme-B (Gzm-B) has an important role in T-cell activation, migration and contraction. However, molecular mechanisms controlling M6PR expression in T cells remain poorly understood. Here, we show that M6PR expression on T cells is distinctively controlled by two common γ-chain cytokines interleukin-2 (IL-2) and IL-7, and the differential M6PR expression is not caused by an altered synthesis of M6PR protein, but is a result of distinct regulation of kinesin-3 motor-protein KIF13A that transport M6PR onto cell surfaces...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28490438/deficiency-in-kinesin-1-recruitment-to-melanosomes-precludes-it-from-facilitating-their-centrifugal-transport
#13
Christopher L Robinson, Richard D Evans, Deborah A Briggs, Jose S Ramalho, Alistair N Hume
Microtubules and F-actin, and associated motor proteins, are considered to play complementary roles in long- and short-range organelle transport. However, there is growing appreciation that myosin/F-actin networks can drive long-range transport. In melanocytes myosin-Va and kinesin-1 have both been proposed as long-range centrifugal melanosome transporters. Here we investigated the role of kinesin-1 heavy chain (Kif5b) and its suggested targeting factor Rab1a in transport. Using confocal microscopy and sub-cellular fractionation we did not detect Kif5b or Rab1a on melanosomes...
May 10, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28489567/eg5-inhibitor-yl001-induces-mitotic-arrest-and-inhibits-tumor-proliferation
#14
Yufei Wang, Xingyu Wu, Mufeng Du, Xi Chen, Xianling Ning, Hong Chen, Siyuan Wang, Jia Liu, Zhenming Liu, Ridong Li, Ge Fu, Chunguang Wang, Michael A McNutt, Demin Zhou, Yuxin Yin
Eg5 is a kinesin spindle protein that controls chromosomal segregation in mitosis and is thus a critical drug target for cancer therapy. We report the discovery of a potent, selective inhibitor of Eg5 designated YL001. YL001 was obtained through shape similarity based virtual screening, and it bears a 1,5-disubstituted tetrazole scaffold. YL001 exhibits favorable bioactivity in a variety of cancer cell lines, including taxol-resistant ovarian cancer and 6TG-resistant breast cancer cell lines. This compound inhibits tumor growth by 60% and significantly prolongs median survival time by more than 50% in a xenograft mouse model...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487562/protein-phosphatase-2a-pp2a-regulates-eg5-to-control-mitotic-progression
#15
Yang Liu, Zhong Zhang, Hui Liang, Xuyang Zhao, Ling Liang, Guangxi Wang, Jingyi Yang, Yan Jin, Michael A McNutt, Yuxin Yin
EG5 (KIF11) is a member of the kinesin-like protein family involved in centrosome separation and bipolar spindle formation. When a cell enters mitosis, CDK1 phosphorylates EG5 at Thr926 and promotes EG5 localization on the mitotic spindle which drives bipolar spindle formation. EG5 provides power for spindle movement and thus controls the dynamics of spindle assembly. However, little is known about EG5 regulation or how EG5 detaches from the spindle upon mitotic exit. In this study we identify EG5 as a novel substrate of PP2A phosphatase, and we show that the PP2A/B55α complex plays an important role in mitotic exit by a mechanism involving EG5...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28485852/vaccinia-virus-proteins-a36-and-f12-e2-show-strong-preferences-for-different-klc-isoforms
#16
William N D Gao, David C J Carpentier, Helen A Ewles, Stacey-Ann Lee, Geoffrey L Smith
Vaccinia virus (VACV) utilises microtubule-mediated trafficking at several stages of its life cycle, of which virus egress is the most intensely studied. During egress VACV proteins A36, F12 and E2 are involved in kinesin-1 interactions, however the roles of these proteins remain poorly understood. A36 forms a direct link between virions and kinesin-1, yet in its absence VACV egress still occurs on microtubules. During a co-immunoprecipitation screen to seek an alternative link between virions and kinesin, A36 was found to bind isoform KLC1 rather than KLC2...
May 9, 2017: Traffic
https://www.readbyqxmd.com/read/28484025/common-general-anesthetic-propofol-impairs-kinesin-processivity
#17
Brandon M Bensel, Stephanie Guzik-Lendrum, Erin M Masucci, Kellie A Woll, Roderic G Eckenhoff, Susan P Gilbert
Propofol is the most widely used i.v. general anesthetic to induce and maintain anesthesia. It is now recognized that this small molecule influences ligand-gated channels, including the GABAA receptor and others. Specific propofol binding sites have been mapped using photoaffinity ligands and mutagenesis; however, their precise target interaction profiles fail to provide complete mechanistic underpinnings for the anesthetic state. These results suggest that propofol and other common anesthetics, such as etomidate and ketamine, may target additional protein networks of the CNS to contribute to the desired and undesired anesthesia end points...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28473757/the-kinesin-adaptor-calsyntenin-1-organizes-microtubule-polarity-and-regulates-dynamics-during-sensory-axon-arbor-development
#18
Tristan J Lee, Jacob W Lee, Elizabeth M Haynes, Kevin W Eliceiri, Mary C Halloran
Axon growth and branching, and development of neuronal polarity are critically dependent on proper organization and dynamics of the microtubule (MT) cytoskeleton. MTs must organize with correct polarity for delivery of diverse cargos to appropriate subcellular locations, yet the molecular mechanisms regulating MT polarity remain poorly understood. Moreover, how an actively branching axon reorganizes MTs to direct their plus ends distally at branch points is unknown. We used high-speed, in vivo imaging of polymerizing MT plus ends to characterize MT dynamics in developing sensory axon arbors in zebrafish embryos...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28473328/tnf%C3%AE-decreases-mitochondrial-movement-in-human-airway-smooth-muscle
#19
Philippe F Delmotte, Vanessa A Zavaletta, Michael A Thompson, Y S Prakash, Gary C Sieck
In airway smooth muscle (ASM) cells, excitation-contraction coupling is accomplished via a cascade of events which connect an elevation of cytosolic Ca(2+) concentration ([Ca(2+)]cyt) with cross-bridge attachment and ATP-consuming mechanical work. Excitation-energy coupling is mediated by linking the elevation in [Ca(2+)]cyt to an increase in mitochondrial Ca(2+) ([Ca(2+)]mito) which in turn stimulates ATP production. Mitochondria proximity with the sarcoplasmic reticulum (SR) and plasma membrane is thought to be an important mechanism to facilitate mitochondrial Ca(2+) uptake...
May 4, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28472620/bidirectionality-from-cargo-thermal-fluctuations-in-motor-mediated-transport
#20
Christopher E Miles, James P Keener
Molecular motor proteins serve as an essential component of intracellular transport by generating forces to haul cargoes along cytoskeletal filaments. Two species of motors that are directed oppositely (e.g. kinesin, dynein) can be attached to the same cargo, which is known to produce bidirectional net motion. Although previous work focuses on the motor number as the driving noise source for switching, we propose an alternative mechanism: cargo diffusion. A mean-field mathematical model of mechanical interactions of two populations of molecular motors with cargo thermal fluctuations (diffusion) is presented to study this phenomenon...
May 1, 2017: Journal of Theoretical Biology
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