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971.
Proteomic screen defines the Polo-box domain interactome and identifies Rock2 as a Plk1 substrate 下载免费PDF全文
Lowery DM Clauser KR Hjerrild M Lim D Alexander J Kishi K Ong SE Gammeltoft S Carr SA Yaffe MB 《The EMBO journal》2007,26(9):2262-2273
Polo-like kinase-1 (Plk1) phosphorylates a number of mitotic substrates, but the diversity of Plk1-dependent processes suggests the existence of additional targets. Plk1 contains a specialized phosphoserine-threonine binding domain, the Polo-box domain (PBD), postulated to target the kinase to its substrates. Using the specialized PBD of Plk1 as an affinity capture agent, we performed a screen to define the mitotic Plk1-PBD interactome by mass spectrometry. We identified 622 proteins that showed phosphorylation-dependent mitosis-specific interactions, including proteins involved in well-established Plk1-regulated processes, and in processes not previously linked to Plk1 such as translational control, RNA processing, and vesicle transport. Many proteins identified in our screen play important roles in cytokinesis, where, in mammalian cells, the detailed mechanistic role of Plk1 remains poorly defined. We go on to characterize the mitosis-specific interaction of the Plk1-PBD with the cytokinesis effector kinase Rho-associated coiled-coil domain-containing protein kinase 2 (Rock2), demonstrate that Rock2 is a Plk1 substrate, and show that Rock2 colocalizes with Plk1 during cytokinesis. Finally, we show that Plk1 and RhoA function together to maximally enhance Rock2 kinase activity in vitro and within cells, and implicate Plk1 as a central regulator of multiple pathways that synergistically converge to regulate actomyosin ring contraction during cleavage furrow ingression. 相似文献
972.
ECM degrading proteases and tissue remodelling in the mammary gland 总被引:12,自引:0,他引:12
Green KA Lund LR 《BioEssays : news and reviews in molecular, cellular and developmental biology》2005,27(9):894-903
Matrix degradation and tissue remodelling directed by matrix-degrading proteases are activated in physiological situations such as wound healing and involution of the prostate, ovaries and uterus. Recently, other activities, in addition to the cleavage of matrix proteins, have been attributed to matrix proteases including the release of growth factors from the extracellular matrix and roles in the maturation of adipocytes. This review describes extracellular proteases, including MMPs, plasminogen and cathepsins involved in the tissue remodelling processes that occur in the breast during pubertal mammary development and the mammary cycle of pregnancy, lactation and weaning. It particularly focuses on development and weaning, termed mammary gland involution, when the majority of remodelling occurs. It also brings together recent findings on the exciting new functions of matrix-degrading proteases. 相似文献
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Martin Lund Kathrine G. Andersen Robert Heaton Iain P. Hargreaves Niels Gregersen Rikke K.J. Olsen 《生物化学与生物物理学报:疾病的分子基础》2021,1867(6):166100
Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is the most common inborn long-chain fatty acid oxidation (FAO) disorder. VLCAD deficiency is characterized by distinct phenotypes. The severe phenotypes are potentially life-threatening and affect the heart or liver, with a comparatively milder phenotype characterized by myopathic symptoms. There is an unmet clinical need for effective treatment options for the myopathic phenotype. The molecular mechanisms driving the gradual decrease in mitochondrial function and associated alterations of muscle fibers are unclear.The peroxisome proliferator-activated receptor (PPAR) pan-agonist bezafibrate is a potent modulator of FAO and multiple other mitochondrial functions and has been proposed as a potential medication for myopathic cases of long-chain FAO disorders. In vitro experiments have demonstrated the ability of bezafibrate to increase VLCAD expression and activity. However, the outcome of small-scale clinical trials has been controversial.We found VLCAD deficient patient fibroblasts to have an increased oxidative stress burden and deranged mitochondrial bioenergetic capacity, compared to controls. Applying heat stress under fasting conditions to bezafibrate pretreated patient cells, caused a marked further increase of mitochondrial superoxide levels. Patient cells failed to maintain levels of the essential thiol peptide antioxidant glutathione and experienced a decrease in cellular viability. Our findings indicate that chronic PPAR activation is a plausible initiator of long-term pathogenesis in VLCAD deficiency. Our findings further implicate disruption of redox homeostasis as a key pathogenic mechanism in VLCAD deficiency and support the notion that a deranged thiol metabolism might be an important pathogenic factor in VLCAD deficiency. 相似文献
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Richard Lund 《Geobios》1984,17(3):281-295
Several specimens of an elasmobranch from the upper Mississippian Bear Gulch limestone of Montana are described. The first dorsal spine and fin closely resemble Stethacanthus erectus and to a lesser extent Stethacanthus altonensis. The new genus and species Orestiacanthus fergusi is proposed for the specimens, and it is suggested that recent attempts to synonymize the species of Stethacanthus on the basis of spines are unjustified. The specimens also share the enlarged cranial denticles, general form of the palatoquadrate, cladodont teeth and pectoral fin with S. altonensis. They differ from S. altonensis in proportions of jaws, numbers of tooth families, numbers of prearticular basals and axial radials, morphology of the second dorsal fin, and in the presence of generalized squamation in some specimens (but not the female). The pelvic fins differ greatly in having a prominent metapterygium. 相似文献