排序方式: 共有207条查询结果,搜索用时 15 毫秒
61.
Plamena R. Angelova Minee L. Choi Alexey V. Berezhnov Mathew H. Horrocks Craig D. Hughes Suman De Margarida Rodrigues Ratsuda Yapom Daniel Little Karamjit S. Dolt Tilo Kunath Michael J. Devine Paul Gissen Mikhail S. Shchepinov Sergiy Sylantyev Evgeny V. Pavlov David Klenerman Andrey Y. Abramov Sonia Gandhi 《Cell death and differentiation》2021,28(5):1755
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Mitogen-activated protein kinases (MAPKs) are a family of proteins that constitute signaling pathways involved in processes that control gene expression, cell division, cell survival, apoptosis, metabolism, differentiation and motility. The MAPK pathways can be divided into conventional and atypical MAPK pathways. The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases, MAPK kinase, and MAPK. Atypical MAPK pathways are not organized into this three-tiered cascade. MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases. The latter are referred to as MAPK-activated protein kinases. This review focuses on one such MAPK-activated protein kinase, MAPK-activated protein kinase 5 (MK5) or p38-regulated/activated protein kinase (PRAK). This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways. Recent findings on the regulation of the activity and subcellular localization, bona fide interaction partners and physiological roles of MK5/PRAK are discussed. 相似文献
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Tadashi Yoshida Sarah Galvez Sumit Tiwari Bashir M. Rezk Laura Semprun-Prieto Yusuke Higashi Sergiy Sukhanov Zipora Yablonka-Reuveni Patrice Delafontaine 《The Journal of biological chemistry》2013,288(33):23823-23832
Cachexia is a serious complication of many chronic diseases, such as congestive heart failure (CHF) and chronic kidney disease (CKD). Although patients with advanced CHF or CKD often have increased angiotensin II (Ang II) levels and cachexia and Ang II causes skeletal muscle wasting in rodents, the potential effects of Ang II on muscle regeneration are unknown. Muscle regeneration is highly dependent on the ability of a pool of muscle stem cells (satellite cells) to proliferate and to repair damaged myofibers or form new myofibers. Here we show that Ang II reduced skeletal muscle regeneration via inhibition of satellite cell (SC) proliferation. Ang II reduced the number of regenerating myofibers and decreased expression of SC proliferation/differentiation markers (MyoD, myogenin, and active-Notch) after cardiotoxin-induced muscle injury in vivo and in SCs cultured in vitro. Ang II depleted the basal pool of SCs, as detected in Myf5nLacZ/+ mice and by FACS sorting, and this effect was inhibited by Ang II AT1 receptor (AT1R) blockade and in AT1aR-null mice. AT1R was highly expressed in SCs, and Notch activation abrogated the AT1R-mediated antiproliferative effect of Ang II in cultured SCs. In mice that developed CHF postmyocardial infarction, there was skeletal muscle wasting and reduced SC numbers that were inhibited by AT1R blockade. Ang II inhibition of skeletal muscle regeneration via AT1 receptor-dependent suppression of SC Notch and MyoD signaling and proliferation is likely to play an important role in mechanisms leading to cachexia in chronic disease states such as CHF and CKD. 相似文献
64.
Torsten H. Walther Christina Gottselig Stephan L. Grage Moritz Wolf Attilio V. Vargiu Marco J. Klein Stefanie Vollmer Sebastian Prock Mareike Hartmann Sergiy Afonin Eva Stockwald Hartmut Heinzmann Olga V. Nolandt Wolfgang Wenzel Paolo Ruggerone Anne S. Ulrich 《Cell》2013,152(1-2):316-326
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65.
Mark P. Little Tamara V. Azizova Dimitry Bazyka Simon D. Bouffler Elisabeth Cardis Sergey Chekin Vadim V. Chumak Francis A. Cucinotta Florent de Vathaire Per Hall John D. Harrison Guido Hildebrandt Victor Ivanov Valeriy V. Kashcheev Sergiy V. Klymenko Olivier Laurent Kotaro Ozasa Soile Tapio Andrew M. Taylor Ioanna Tzoulaki Wendy L. Vandoolaeghe Richard Wakeford Lydia Zablotska Wei Zhang Steven E. Lipshultz 《Radiation and environmental biophysics》2013,52(1):157-159
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Kevin Hannigan Shridhar S. Kulkarni Volodymyr G. Bdzhola Andriy G. Golub Sergiy M. Yarmoluk Tanaji T. Talele 《Bioorganic & medicinal chemistry letters》2013,23(21):5790-5794
Poly(ADP-ribose)polymerase-1 (PARP-1) is an abundant and ubiquitous chromatin-bound nuclear protein. PARP-1, a DNA repair enzyme, has been in the limelight as a chemotherapeutic target. In this study, we demonstrated the successful use of structure-based virtual screening to identify inhibitors of PARP-1 from Otava databases comprised of nearly 260,000 compounds. Five novel inhibitors belonging to thienopyrimidinone, isoquinolinoquinazolinone, pyrroloquinazolinone, and cyclopentenothienopyrimidinone scaffolds revealed inhibitory potencies with IC50 values ranged from 9.57 μM to 0.72 μM. Structural features relevant to the activity of these novel compounds within the active site of PARP-1 are discussed in detail and will guide future SAR investigation on these scaffolds. 相似文献
67.
Golub AG Bdzhola VG Kyshenia YV Sapelkin VM Prykhod'ko AO Kukharenko OP Ostrynska OV Yarmoluk SM 《Molecular and cellular biochemistry》2011,356(1-2):107-115
Serine/threonine protein kinase CK2 controls vast variety of fundamental processes in cell life; however, despite long period of study, its functional role is not completely determined. CK2 has a significant pathogenic potential and its activity is strictly associated with the development of various kinds of disorders. There are a growing number of facts that inhibitors of CK2 could be used as pharmaceutical agents for the cancer treatment, viral infections, and inflammatory diseases. In this article, we report structural and biological data on the novel synthetic flavonol derivatives, 3-hydroxy-4'-carboxyflavones, possessing a high inhibitory activity toward CK2. With the aid of combinatorial organic synthesis, molecular modeling techniques and biochemical in vitro tests, we studied the structure-activity relationships of flavonol derivatives and developed binding model describing their key intermolecular interactions with the CK2 ATP-binding site. Obtained data show that the synthetic 3-hydroxy-4'-carboxyflavones possess the highest activity among flavonol inhibitors of CK2 known till date. 相似文献
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Dorr CR Yemets S Kolomitsyna O Krasutsky P Mansky LM 《Bioorganic & medicinal chemistry letters》2011,21(1):542-545
Triterpene derivatives were analyzed for anti-HIV-1 activity and for cellular toxicity. Betulinic aldehyde, betulinic nitrile, and morolic acid derivatives were identified to have anti-HIV-1 activity. These derivatives inhibit a late step in virus replication, likely virus maturation. 相似文献
70.
Dmitriev OY Bhattacharjee A Nokhrin S Uhlemann EM Lutsenko S 《The Journal of biological chemistry》2011,286(18):16355-16362
Wilson disease (WD) is a disorder of copper metabolism caused by mutations in the Cu-transporting ATPase ATP7B. WD is characterized by significant phenotypic variability, the molecular basis of which is poorly understood. The E1064A mutation in the N-domain of ATP7B was previously shown to disrupt ATP binding. We have now determined, by NMR, the structure of the N-domain containing this mutation and compared properties of E1064A and H1069Q, another mutant with impaired ATP binding. The E1064A mutation does not change the overall fold of the N-domain. However, the position of the α1,α2-helical hairpin (α-HH) that houses Glu(1064) and His(1069) is altered. The α-HH movement produces a more open structure compared with the wild-type ATP-bound form and misaligns ATP coordinating residues, thus explaining complete loss of ATP binding. In the cell, neither the stability nor targeting of ATP7B-E1064A to the trans-Golgi network differs significantly from the wild type. This is in a contrast to the H1069Q mutation within the same α-HH, which greatly destabilizes protein both in vitro and in cells. The difference between two mutants can be linked to a lower stability of the α-HH in the H1069Q variant at the physiological temperature. We conclude that the structural stability of the N-domain rather than the loss of ATP binding plays a defining role in the ability of ATP7B to reach the trans-Golgi network, thus contributing to phenotypic variability in WD. 相似文献