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991.
992.
A Small GTPase Activator Protein Interacts with Cytoplasmic Phytochromes in Regulating Root Development 总被引:1,自引:0,他引:1
Dong Ho Shin Man-Ho Cho Tae-Lim Kim Jihye Yoo Jeong-Il Kim Yun-Jeong Han Pill-Soon Song Jong-Seong Jeon Seong Hee Bhoo Tae-Ryong Hahn 《The Journal of biological chemistry》2010,285(42):32151-32159
Phytochromes enable plants to sense light information and regulate developmental responses. Phytochromes interact with partner proteins to transmit light signals to downstream components for plant development. PIRF1 (phytochrome-interacting ROP guanine-nucleotide exchange factor (RopGEF 1)) functions as a light-signaling switch regulating root development through the activation of ROPs (Rho-like GTPase of plant) in the cytoplasm. In vitro pulldown and yeast two-hybrid assays confirmed the interaction between PIRF1 and phytochromes. PIRF1 interacted with the N-terminal domain of phytochromes through its conserved PRONE (plant-specific ROP nucleotide exchanger) region. PIRF1 also interacted with ROPs and activated them in a phytochrome-dependent manner. The Pr form of phytochrome A enhanced the RopGEF activity of PIRF1, whereas the Pfr form inhibited it. A bimolecular fluorescence complementation analysis demonstrated that PIRF1 was localized in the cytoplasm and bound to the phytochromes in darkness but not in light. PIRF1 loss of function mutants (pirf1) of Arabidopsis thaliana showed a longer root phenotype in the dark. In addition, both PIRF1 overexpression mutants (PIRF1-OX) and phytochrome-null mutants (phyA-211 and phyB-9) showed retarded root elongation and irregular root hair formation, suggesting that PIRF1 is a negative regulator of phytochrome-mediated primary root development. We propose that phytochrome and ROP signaling are interconnected through PIRF1 in regulating the root growth and development in Arabidopsis. 相似文献
993.
Sunggeon Ko Gil Bu Kang Sung Min Song Jung-Gyu Lee Dong Yeon Shin Ji-Hye Yun Yi Sheng Chaejoon Cheong Young Ho Jeon Yong-Keun Jung Cheryl H. Arrowsmith George V. Avvakumov Sirano Dhe-Paganon Yung Joon Yoo Soo Hyun Eom Weontae Lee 《The Journal of biological chemistry》2010,285(46):36070-36080
E2–25K/Hip2 is an unusual ubiquitin-conjugating enzyme that interacts with the frameshift mutant of ubiquitin B (UBB+1) and has been identified as a crucial factor regulating amyloid-β neurotoxicity. To study the structural basis of the neurotoxicity mediated by the E2–25K-UBB+1 interaction, we determined the three-dimensional structures of UBB+1, E2–25K and the E2–25K/ubiquitin, and E2–25K/UBB+1 complex. The structures revealed that ubiquitin or UBB+1 is bound to E2–25K via the enzyme MGF motif and residues in α9 of the enzyme. Polyubiquitylation assays together with analyses of various E2–25K mutants showed that disrupting UBB+1 binding markedly diminishes synthesis of neurotoxic UBB+1-anchored polyubiquitin. These results suggest that the interaction between E2–25K and UBB+1 is critical for the synthesis and accumulation of UBB+1-anchored polyubiquitin, which results in proteasomal inhibition and neuronal cell death. 相似文献
994.
We have shown that protein kinase CKII (CKII) inhibition induces senescence through the p53-dependent pathway in HCT116 cells. Here we examined the molecular mechanism through which CKII inhibition activates p53 in HCT116 cells. CKII inhibition by treatment with CKII inhibitor or CKIIα small-interfering RNA (siRNA) increased intracellular hydrogen peroxide and superoxide anion levels. These effects were significantly blocked by pretreatment of cells with the antioxidant N-acetylcysteine. Additionally, NADPH oxidase (NOX) inhibitor apocynin and p22phox siRNA significantly reduced p53 expression and suppressed the appearance of senescence markers. CKII inhibition did not affect mitochondrial superoxide generation. These data demonstrate that CKII inhibition induces superoxide anion generation via NOX activation, and subsequent superoxide-dependent activation of p53 acts as a mediator of senescence in HCT116 cells after down-regulation of CKII. 相似文献
995.
Soh-Hyun Lee Sun-Ok Ha Ho-Jin Koh KilSoo Kim Seon-Min Jeon Myung-Sook Choi Oh-Shin Kwon Tae-Lin Huh 《Molecules and cells》2010,29(2):203-208
Hyperglycemia-induced oxidative stress is widely recognized as a key mediator in the pathogenesis of diabetic nephropathy,
a complication of diabetes. We found that both expression and enzymatic activity of cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) were upregulated in the renal cortexes of diabetic rats and mice. Similarly, IDPc
was induced in murine renal proximal tubular OK cells by high hyperglycemia, while it was abrogated by co-treatment with the
antioxidant N-Acetyl-Cysteine (NAC). In OK cells, increased expression of IDPc by stable transfection prevented hyperglycemia-mediated
reactive oxygen species (ROS) production, subsequent cellular oxidative stress and extracellular matrix accumulation, whereas
these processes were all stimulated by decreased IDPc expression. In addition, production of NADPH and GSH in the cytosol
was positively correlated with the expression level of IDPc in OK cells. These results together indicate that upregulation
of IDPc in response to hyperglycemia might play an essential role in preventing the progression of diabetic nephropathy, which
is accompanied by ROS-induced cellular damage and fibrosis, by providing NADPH, the reducing equivalent needed for recycling
reduced glutathione and low molecular weight antioxidant thiol proteins. 相似文献
996.
997.
998.
Oh KB Jeon HB Han YR Lee YJ Park J Lee SH Yang D Kwon M Shin J Lee HS 《Bioorganic & medicinal chemistry letters》2010,20(22):6644-6648
A new series of bromophenols was synthesized by reactions of corresponding phenol analogs with bromine. The synthesized compounds were tested for inhibitory activity against isocitrate lyase (ICL) of Candida albicans and antimicrobial activity against gram-positive and, gram-negative bacteria and fungi. Among the synthesized bromophenols, bis(3-bromo-4,5-dihydroxyphenyl)methanone (11) and (3-bromo-4,5-dihydroxyphenyl)(2,3-dibromo-4,5-dihydroxyphenyl)methanone (12) displayed potent inhibitory activities against ICL, showing a stronger inhibitory effects than were found with natural bromophenol 1. The preliminary structure-activity relationships were investigated in order to determine the essential structural requirements for the inhibitory activities of these compounds against ICL of C. albicans. 相似文献
999.
Somin Lee Minhwan Chung Seung-Ryeol Lee Noo Li Jeon 《Biotechnology and bioengineering》2020,117(3):i-i
The human central nervous system (CNS) vasculature expresses a distinctive barrier phenotype, the blood–brain barrier (BBB). As the BBB contributes to low efficiency in CNS pharmacotherapy by restricting drug transport, the development of an in vitro human BBB model has been in demand. Here, we present a microfluidic model of CNS angiogenesis having three-dimensional (3D) lumenized vasculature in concert with perivascular cells. We confirmed the necessity of the angiogenic tri-culture system (brain endothelium in direct interaction with pericytes and astrocytes) to attain essential phenotypes of BBB vasculature, such as minimized vessel diameter and maximized junction expression. In addition, lower vascular permeability is achieved in the tri-culture condition compared to the monoculture condition. Notably, we focussed on reconstituting the functional efflux transporter system, including p-glycoprotein (p-gp), which is highly responsible for restrictive drug transport. By conducting the calcein-AM efflux assay on our 3D perfusable vasculature after treatment of efflux transporter inhibitors, we confirmed the higher efflux property and prominent effect of inhibitors in the tri-culture model. Taken together, we designed a 3D human BBB model with functional barrier properties based on a developmentally inspired CNS angiogenesis protocol. We expect the model to contribute to a deeper understanding of pathological CNS angiogenesis and the development of effective CNS medications. 相似文献
1000.
Shinrye Lee Yu-Mi Jeon Sun Joo Cha Seyeon Kim Younghwi Kwon Myungjin Jo 《Autophagy》2020,16(8):1396-1412
ABSTRACT TARDBP/TDP-43 (TAR DNA binding protein) proteinopathies are a common feature in a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and Alzheimer disease (AD). However, the molecular mechanisms underlying TARDBP-induced neurotoxicity are largely unknown. In this study, we demonstrated that TARDBP proteinopathies induce impairment in the ubiquitin proteasome system (UPS), as evidenced by an accumulation of ubiquitinated proteins and a reduction in proteasome activity in neuronal cells. Through kinase inhibitor screening, we identified PTK2/FAK (PTK2 protein tyrosine kinase 2) as a suppressor of neurotoxicity induced by UPS impairment. Importantly, PTK2 inhibition significantly reduced ubiquitin aggregates and attenuated TARDBP-induced cytotoxicity in a Drosophila model of TARDBP proteinopathies. We further identified that phosphorylation of SQSTM1/p62 (sequestosome 1) at S403 (p-SQSTM1 [S403]), a key component in the autophagic degradation of poly-ubiquitinated proteins, is increased upon TARDBP overexpression and is dependent on the activation of PTK2 in neuronal cells. Moreover, expressing a non-phosphorylated form of SQSTM1 (SQSTM1S403A) significantly repressed the accumulation of insoluble poly-ubiquitinated proteins and neurotoxicity induced by TARDBP overexpression in neuronal cells. In addition, TBK1 (TANK binding kinase 1), a kinase that phosphorylates S403 of SQSTM1, was found to be involved in the PTK2-mediated phosphorylation of SQSTM1. Taken together, our data suggest that the PTK2-TBK1-SQSTM1 axis plays a critical role in the pathogenesis of TARDBP by regulating neurotoxicity induced by UPS impairment. Therefore, targeting the PTK2-TBK1-SQSTM1 axis may represent a novel therapeutic intervention for neurodegenerative diseases with TARDBP proteinopathies.Abbreviations: ALP: macroautophagy/autophagy lysosomal pathway; ALS: amyotrophic lateral sclerosis; ATXN2: ataxin 2; BafA1: bafilomycin A1; cCASP3: cleaved caspase 3; CSNK2: casein kinase 2; FTLD: frontotemporal lobar degeneration; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; OPTN: optineurin; PTK2/FAK: PTK2 protein tyrosine kinase 2; SQSTM1/p62: sequestosome 1; TARDBP/TDP-43: TAR DNA binding protein; TBK1: TANK binding kinase 1; ULK1: unc-51 like autophagy activating kinase 1; UPS: ubiquitin-proteasome system. 相似文献