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Neurochemical Research - Post-translational modification (PTMs) of proteins by ubiquitin and ubiquitin-like modifiers such as interferon-stimulated gene 15 (ISG15) and small ubiquitin-related... 相似文献
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Proteins from thermophilic microorganisms are stabilized by various mechanisms to preserve their native folded states at higher
temperatures. A thermostable glucose-6-phosphate dehydrogenase (tG6PDH) from the hyperthermophilic bacterium Aquifex aeolicus was expressed as a recombinant protein in Escherichia coli. The A. aeolicus G6PDH is a homodimer exhibiting remarkable thermostability (t1/2=24 hr at 90°C). Based on homology modeling and upon comparison of its structure with human G6PDH, it was predicted that cysteine
184 of one subunit could form a disulfide bond with cysteine 352 of the other subunit resulting in reinforced intersubunit
interactions that hold the dimer together. Site-directed mutagenesis was performed on tG6PDH to convert C184 and C352 to serines.
The tG6PDH double mutant exhibited a dramatic decrease in the half-life from 24 hr to 3 hr at 90°C. The same decrease in half-life
was also found when either C184 or C352 was mutated to serine. The result indicates that C184 and C352 may play a crucial
role in strengthening the dimer interface through disulfide bond formation, thereby contributing to the thermal stability
of the enzyme. 相似文献
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The orchestration of the events in the cell during the progression of the cell cycle is modulated by various phenomenon which are regulated by structural modules of the cell. The nucleus is a major hub for all these regulatory units which harbour the nuclear matrix, matrix proteins and chromatin. The histone modifications etch a complex code on the chromatin and the matrix proteins in consort with the histone code regulate the gene expression. SMAR1 is a matrix attachment region binding protein that interacts with chromatin modulators like HDAC1, Sin3A and causes chromatin condensation. SMAR1 modulates the chromatin at the Vβ locus and plays a prominent role in V(D)J recombination. Such indispensable function of SMAR1 by the modulation of chromatin in the context of malignancy and V(D)J recombination emphasizes that MAR binding proteins regulate the complex events of the cell and perturbed expression causes disease conditions. 相似文献
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Molecular Mechanisms of Apoptosis in Cerebral Ischemia: Multiple Neuroprotective Opportunities 总被引:3,自引:0,他引:3
Cerebral ischemia/reperfusion (I/R) injury triggers multiple and distinct but overlapping cell signaling pathways, which may
lead to cell survival or cell damage. There is overwhelming evidence to suggest that besides necrosis, apoptosis do contributes
significantly to the cell death subsequent to I/R injury. Both extrinsic and intrinsic apoptotic pathways play a vital role,
and upon initiation, these pathways recruit downstream apoptotic molecules to execute cell death. Caspases and Bcl-2 family
members appear to be crucial in regulating multiple apoptotic cell death pathways initiated during I/R. Similarly, inhibitor
of apoptosis family of proteins (IAPs), mitogen-activated protein kinases, and newly identified apoptogenic molecules, like
second mitochondrial-activated factor/direct IAP-binding protein with low pI (Smac/Diablo), omi/high-temperature requirement serine protease A2 (Omi/HtrA2), X-linked mammalian inhibitor of apoptosis
protein-associated factor 1, and apoptosis-inducing factor, have emerged as potent regulators of cellular apoptotic/antiapoptotic
machinery. All instances of cell survival/death mechanisms triggered during I/R are multifaceted and interlinked, which ultimately
decide the fate of brain cells. Moreover, apoptotic cross-talk between major subcellular organelles suggests that therapeutic
strategies should be optimally directed at multiple targets/mechanisms for better therapeutic outcome. Based on the current
knowledge, this review briefly focuses I/R injury-induced multiple mechanisms of apoptosis, involving key apoptotic regulators
and their emerging roles in orchestrating cell death programme. In addition, we have also highlighted the role of autophagy
in modulating cell survival/death during cerebral ischemia. Furthermore, an attempt has been made to provide an encouraging
outlook on emerging therapeutic approaches for cerebral ischemia.
Venkata Prasuja Nakka and Anchal Gusain equally contributed to this work. 相似文献
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Amar S. Godar Vijaya K. Varanasi Sridevi Nakka P. V. Vara Prasad Curtis R. Thompson J. Mithila 《PloS one》2015,10(5)
Herbicide efficacy is known to be influenced by temperature, however, underlying mechanism(s) are poorly understood. A marked alteration in mesotrione [a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor] efficacy on Palmer amaranth (Amaranthus palmeri S. Watson) was observed when grown under low- (LT, 25/15°C, day/night temperatures) and high (HT, 40/30°C) temperature compared to optimum (OT, 32.5/22.5°C) temperature. Based on plant height, injury, and mortality, Palmer amaranth was more sensitive to mesotrione at LT and less sensitive at HT compared to OT (ED50 for mortality; 18.5, 52.3, and 63.7 g ai ha-1, respectively). Similar responses were observed for leaf chlorophyll index and photochemical efficiency of PSII (Fv/Fm). Furthermore, mesotrione translocation and metabolism, and HPPD expression data strongly supported such variation. Relatively more mesotrione was translocated to meristematic regions at LT or OT than at HT. Based on T50 values (time required to metabolize 50% of the 14C mesotrione), plants at HT metabolized mesotrione faster than those at LT or OT (T50; 13, 21, and 16.5 h, respectively). The relative HPPD:CPS (carbamoyl phosphate synthetase) or HPPD:β-tubulin expression in mesotrione-treated plants increased over time in all temperature regimes; however, at 48 HAT, the HPPD:β-tubulin expression was exceedingly higher at HT compared to LT or OT (18.4-, 3.1-, and 3.5-fold relative to untreated plants, respectively). These findings together with an integrated understanding of other interacting key environmental factors will have important implications for a predictable approach for effective weed management. 相似文献
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S Senthilvel B Jayashree V Mahalakshmi P Sathish Kumar S Nakka T Nepolean CT Hash 《BMC plant biology》2008,8(1):119