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Src Protein Tyrosine Kinases in Stress Responses
Grishin, Anatoly,Corey, Seth J. The Korean Society for Integrative Biology 2002 Korean journal of biological sciences Vol.6 No.1
A role of Src family protein Tyrosine kinases (SFK) as mediators of receptor-ligand initiated responses is well established. Well documented, but less well understood is the role of SFK in cellular reaction to stresses. Evidence from the wide variety of experimental systems indicates that SFK mediate responses to all major classes of stress, including oxidation, DNA damage, mechanical impacts, and protein denaturing. SFK may be activated by stresses directly or via regulatory circuits whose identity is not yet fully understood. Depending on the cell type and the nature of activating stimulus, SFK may activate known downstream signaling cascades leading to cell survival, proliferation, cytoskeletal rearrangement, and apoptosis; the identity of these cascades is discussed. As in the case of receptor-initiated signaling, roles of individual SFK in various stress response may be redundant or non-redundant. Although signals generated by different stresses are generally transduced via distinct SFK pathways, these pathways may overlap or exhibit crosstalk. In some cell types stress-induced activation of SFK promotes survival and inhibits apoptosis, whereas the opposite may be true for other cell types. Stress responses constitute a new and rapidly developing area of SFK-mediated signaling.
Dmitrii Ludin,Yulia Voitovich,Evgenia Salomatina,Yulia Kuznetsova,Ivan Grishin,Igor Fedushkin,Sergey Zaitsev 한국고분자학회 2020 Macromolecular Research Vol.28 No.9
We report a reversible-deactivation radical copolymerization of styrene and methyl acrylate in the presence of tributylborane and different p-quinones. p-Quinones, such as 1,4-naphthoquinone, 2,3-dimethyl-1,4-benzoquinone, 2,5-ditert- 1,4-butylbenzoquinone, and duroquinone, with addition of a catalytic amount of tributylborane, allow for the control over styrene/methyl acrylate copolymerization. The process proceeds in a controlled manner via a reversible homolytic dissociation of the active macromolecules with terminal aryloxyboron-groups. The rate of styrene/methyl acrylate copolymerization depends on the inhibition constants of quinones. The molecular weight and molecular weight distribution of copolymers are directly dependent on the inhibitory abilities of the quinones. 1,4-Naphthoquinone and 2,3-dimethyl-1,4-benzoquinone act as the most effective mediators of chain propagation. Matrixassisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) results showed that the macromolecules contained internal fragments of p-quinone. Also, of the terminal aryloxyboron-groups were detected in the mass spectra. On realization of the “living” mechanism of copolymerization, the structure of copolymers obtained at high conversions can be considered as similar to the gradient structure. Stereo-regularity of the copolymers differed from the conventional radical copolymerization. The glass-transition temperature (Tg) of the gradient copolymer differed from Tg of the random compositional heterogeneous copolymer. The effect of the macromolecular structure on the mechanical properties of the copolymers was studied.
Truncated Adenomatous Polyposis Coli Mutation Induces Asef-Activated Golgi Fragmentation
Kim, Sang Bum,Zhang, Lu,Yoon, Jimok,Lee, Jeon,Min, Jaewon,Li, Wenlin,Grishin, Nick V.,Moon, Young-Ah,Wright, Woodring E.,Shay, Jerry W. American Society for Microbiology 2018 Molecular and cellular biology Vol.38 No.17
<P>Adenomatous polyposis coli (APC) is a key molecule to maintain cellular homeostasis in colonic epithelium by regulating cell-cell adhesion, cell polarity, and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (Asef). The APC-activated Asef stimulates the small GTPase, which leads to decreased cell-cell adherence and cell polarity, and enhanced cell migration. In colorectal cancers, while truncated APC constitutively activates Asef and promotes cancer initiation and progression, regulation of Asef by full-length APC is still unclear. Here, we report the autoinhibition mechanism of full-length APC. We found that the armadillo repeats in full-length APC interact with the APC residues 1362 to 1540 (APC-2,3 repeats), and this interaction competes off and inhibits Asef. Deletion of APC-2,3 repeats permits Asef interactions leading to downstream signaling events, including the induction of Golgi fragmentation through the activation of the Asef-ROCK-MLC2. Truncated APC also disrupts protein trafficking and cholesterol homeostasis by inhibition of SREBP2 activity in a Golgi fragmentation-dependent manner. Our study thus uncovers the autoinhibition mechanism of full-length APC and a novel gain of function of truncated APC in regulating Golgi structure, as well as cholesterol homeostasis, which provides a potential target for pharmaceutical intervention against colon cancers.</P>
Dmitrii V. Ludin,Nadezhda V. Illarionova,Ekaterina V. Bobrina,Konstantin A. Kozhanov,Ivan D. Grishin,Sergey D. Zaitsev,Igor L. Fedushkin 한국고분자학회 2023 Macromolecular Research Vol.31 No.3
Polymerization of styrene with tributylborane in the presence of various p-quinones (2,3-dimethyl-1,4-benzoquinone, 1,4-naphthoquinone, menadione, duroquinone, 2,5-di-tert-butyl-1,4-benzoquinone) has been investigated. It was found that in spite of dual nature of p-quinone and the presence of tributylborane in the initial mixture, the semi-quinone macroradical is capable to “chain regeneration”. Neither solvent introduction nor use of a more reactive triethylborane affects this process. The insensitivity of this reaction to external conditions may be caused by the cell effect. For some p-quinones in the presence of tributylborane, the realization of reversible-deactivation radical polymerization is observed. Mechanism of the chain termination reactions was established by the MALDI-TOF technique. It consists of reversible inhibition causing the formation of active macromolecules as well as irreversible inhibition causing the formation of “dead” macromolecules. The ratio of these directions depends on the relative reactivity of p-quinone (kz/kp). The higher is kz/kp, the lower is the probability of irreversible inhibition. Polymers obtained in the presence of the tributylborane/p-quinone system can re-initiate polymerization. Post-polymers with distinct molecular weight characteristics (Đ = 1.12 – 1.19) were obtained during this synthesis. Only polystyrene macro-radicals are formed during polymerization re-initiation. This fact has been proven by ESR spectroscopy. The macroinitiator polymers isolated at the initial conversions have the same reactivity regardless of the p-quinone nature. The linear dependence of Mn with conversion, the polydispersity lessening, and the constant concentration of macro-radicals indicate realization of reversible-deactivation radical polymerization.
New Derivatives of Natural Acyclic Guanidine Alkaloids with TRPV Receptor-Regulating Properties
Ogurtsova, Ekaterina K.,Makarieva, Tatyana N.,Korolkova, Yuliya V.,Andreev, Yaroslav A.,Mosharova, Irina V.,Denisenko, Vladimir A.,Dmitrenok, Pavel S.,Lee, Yeon-Ju,Grishin, Eugene V.,Stonik, Valentin NATURAL PRODUCT COMMUNICATIONS 2015 Natural product communications Vol.10 No.7