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51.
Andreas Ritter Mourad Sanhaji Alexandra Friemel Susanne Roth Udo Rolle Frank Louwen Juping Yuan 《Cell cycle (Georgetown, Tex.)》2015,14(23):3755-3767
Mitotic centromere-associated kinesin (MCAK) is the best characterized member of the kinesin-13 family and plays important roles in microtubule dynamics during mitosis. Its activity and subcellular localization is tightly regulated by an orchestra of mitotic kinases, such as Aurora B. It is well known that serine 196 of MCAK is the major phosphorylation site of Aurora B in Xenopus leavis extracts and that this phosphorylation regulates its catalytic activity and subcellular localization. In the current study, we have addressed the conserved phosphorylation site serine 192 in human MCAK to characterize its function in more depth in human cancer cells. Our data confirm that S192 is the major phosphorylation site of Aurora B in human MCAK and that this phosphorylation has crucial roles in regulating its catalytic activity and localization at the kinetochore/centromere region in mitosis. Interfering with this phosphorylation leads to a delayed progression through prometa- and metaphase associated with mitotic defects in chromosome alignment and segregation. We show further that MCAK is involved in directional migration and invasion of tumor cells, and interestingly, interference with the S192 phosphorylation affects this capability of MCAK. These data provide the first molecular explanation for clinical observation, where an overexpression of MCAK was associated with lymphatic invasion and lymph node metastasis in gastric and colorectal cancer patients. 相似文献
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So Jeong Park Doo Ri Park Deepak Bhattarai Kyeong Lee Jaesang Kim Yun Soo Bae Soo Young Lee 《Molecules and cells》2014,37(8):628-635
2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity. 相似文献
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Using cub growth as an index, I examine the influence of maternalnutrition, litter size, and cub sex on maternal care in cheetahs(Acinonyx jubatus) and compare cub and litter growth rates withthose of other large feilds. Seventy-nine free-living cheetahcubs in 21 litters from 15 mothers were weighed at least oncebetween 6 and 48 days of age. Eleven litters were weighed atthe beginning and end of a 5-day observation of their mothers.The mean cub growth rate varied significantly between litters,due primarily to differences in maternal food intake. Growthdeclined sharply when maternal food intake was less than 1.5kg/ day, but did not increase with greater levels of food intake.Lower limits of growth rates may therefore have been set bythe mother's food intake, whereas upper limits may be set bythe intrinsic physiological ability of cubs to grow. Althoughmale cubs were heavier than female cubs in the same litter whenfirst weighed, major differences in growth rate between thesexes were not apparent at this stage. Both cheetah cubs andlitters grow fast relative to other large felids, and I arguethat this may be an adaptation to the high rate of cheetah juvenilemortality from predation. 相似文献
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An A in equilibrium with G transition in exon III is known to differentiate alleles A and B of the cattle beta-lactoglobulin (BLG) gene. A BLG exon III fragment containing the transition site was amplified by the polymerase chain reaction. Temperature gradient gel electrophoresis (TGGE) was then used to detect this transition and hence to genotype cattle: the AT base-pair in allele A was readily distinguished from the GC base-pair of allele B. TGGE can be used to detect any single base-pair substitution, and thus is a powerful method of detecting genetic variability. 相似文献
58.
Phytochrome A is readily cleavable by proteolytic agents to yield an amino-terminal fragment of 66 kilodalton (kDa), which
consists of residues 1 to approximately 600, and a dimer of the carboxy-terminal 55-kDa fragment, from residue 600 or so to
the carboxyl terminus. The former domain, carrying the tetrapyrrole chromophore, has been studied extensively because of its
photoactivity, while less attention has been paid to the non-chromophoric portion until quite recently. However, the evidence
gathered to date suggests that this domain is also of great improtance. We present here a review of the structure and the
biochemical and physiological functions of the two domains, of parts of these domains, and of the cooperation between them. 相似文献
59.
《Cell calcium》2018
Store-operated calcium entry (SOCE) is the flow of calcium ions (Ca2+) into cells in response to the depletion of intracellular Ca2+ stores that reside predominantly in the endoplasmic reticulum (ER). The role of SOCE has been relatively well understood for non-excitable cells. It is mediated mostly by the ER Ca2+ sensor STIM1 and plasma membrane Ca2+ channel Orai1 and serves to sustain Ca2+ signaling and refill ER Ca2+ stores. In contrast, because of the complexity of Ca2+ influx mechanisms that are present in excitable cells, our knowledge about the function of neuronal SOCE (nSOCE) is still nascent. This review summarizes the available data on the molecular components of nSOCE and their relevance to neuronal signaling. We also present evidence of disturbances of nSOCE in neurodegenerative diseases (namely Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease) and traumatic brain injury. The emerging important role of nSOCE in neuronal physiology and pathology makes it a possible clinical target. 相似文献
60.