Regulation of the stability and transcriptional activity of NFATc4 by ubiquitination

AbstractNuclear factor of activated T cells (NFATc4) has been implicated as a critical regulator of the cardiac development and hypertrophy. However, the mechanisms for regulating NFATc4 stability and transactivation remain unclear. We showed that NFATc4 protein was predominantly ubiquitinated through the formation of Lysine 48-linked polyubiquitin chains, and this modification decreased NFATc4 protein levels and its transcriptional activity. Furthermore, activation of GSK3β markedly enhanced NFATc4 ubiquitination and decreased its transactivation, whereas inhibition of GSK3β had opposite effects. Importantly, ubiquitination and phosphorylation induced by GSK3β repressed NFATc4-dependent cardiac-specific gene expression. These results demonstrate that the ubiquitin–proteasome system plays an important role in regulating NFATc4 stability and transactivation.Structured summaryMINT-6798349:NFATc4 (uniprotkb:Q14934) physically interacts (MI:0218) with Ubiquitin (uniprotkb:P62988) by anti bait coimmunoprecipitation (MI:0006)MINT-6798334:NFATc4 (uniprotkb:Q14934) physically interacts (MI:0218) with Ubiquitin (uniprotkb:P62988) by anti tag coimmunoprecipitation (MI:0007)MINT-6798321:Ubiquitin (uniprotkb:P62988) physically interacts (MI:0218) with NFATc4 (uniprotkb:Q14934) by pull down (MI:0096

C Terminus of Hsc70-interacting Protein Promotes Smooth Muscle Cell Proliferation and Survival through Ubiquitin-mediated Degradation of FoxO1

Forkhead transcription factors (FoxOs) play a pivotal role in controlling cellular proliferation and survival. The cellular level of these factors is tightly regulated through the phosphoinositide 3-kinase/Akt and ubiquitin-mediated degradation. However, the ubiquitin ligases responsible for the degradation of FoxO1 and the relevance of this regulation to smooth muscle cell (SMC) proliferation and survival have not been fully identified. Here we showed that overexpression of C terminus of Hsc70-interacting protein (CHIP) promoted ubiquitination and degradation of FoxO1 in SMCs in response to tumor necrosis factor-α. Both the U-box (containing ubiquitin ligase activity) and the charged (essential for FoxO1 binding) domains within CHIP were required for CHIP-mediated FoxO1 down-regulation. Moreover, interaction and ubiquitination of FoxO1 by CHIP depended on phos pho ryl a tion of FoxO1 at Ser-256. Furthermore, overexpression of CHIP repressed FoxO1-mediated transactivation and its proapo pto tic function following tumor necrosis factor-α treatment. In contrast, knockdown of CHIP by small interfering RNA enhanced FoxO1-mediated transactivation and its effect on SMC proliferation and survival. Taken together, our data indicate that CHIP is a negative regulator of FoxO1 activity through ubiquitin-mediated degradation, and inhibition of CHIP may serve as a potential therapeutic target for reducing proliferative arterial diseases

Bioactivities and Future Perspectives of Chaetoglobosins

Chaetoglobosins belonging to cytochalasan alkaloids represent a large class of fungal secondary metabolites. To date, around 100 chaetoglobosins and their analogues have been isolated and identified over the years from a variety of fungi, mainly from the fungus Chaetomium globosum. Studies have found that chaetoglobosins possess a broad range of biological activities, including antitumor, antifungal, phytotoxic, fibrinolytic, antibacterial, nematicidal, anti-inflammatory, and anti-HIV activities. This review will comprehensively summarize the biological activities and mechanisms of action of nature-derived chaetoglobosins

The Effect of Ethanol on Abnormal Grain Growth in Copper Foils

Single-crystal Cu not only has high electrical and thermal conductivity, but can also be used as a promising platform for the epitaxial growth of two-dimensional materials. Preparing large-area single-crystal Cu foils from polycrystalline foils has emerged as the most promising technique in terms of its simplicity and effectiveness. However, the studies on transforming polycrystalline foil into large-area single-crystal foil mainly focus on the influence of annealing temperature and strain energy on the recrystallization process of copper foil, while studies on the effect of annealing atmosphere on abnormal grain growth behavior are relatively rare. It is necessary to carry out more studies on the effect of annealing atmosphere on grain growth behavior to understand the recrystallization mechanism of metal. Here, we found that introduction of ethanol in pure argon annealing atmosphere will cause the abnormal grain growth of copper foil. Moreover, the number of abnormally grown grains can be controlled by the concentration of ethanol in the annealing atmosphere. Using this technology, the number of abnormally grown grains on the copper foil can be controlled to single one. This abnormally grown grain will grow rapidly to decimeter-size by consuming the surrounding small grains. This work provides a new perspective for the understanding of the recrystallization of metals, and a new method for the preparation of large-area single-crystal copper foils

Proportional Fair Scheduling for Downlink mmWave Multi-User MISO-NOMA Systems

International audienceIn this paper, we study non-orthogonal multiple access (NOMA) user scheduling and resource allocation problem for a generic downlink single-cell multiple input and single output (MISO) millimeter wave (mmWave) system. The larger number of packed antennas and the highly directional property of mmWave communications enable directional beamforming to achieve spatial diversity. Toward this end, we consider two different hybrid precoding schemes which are based on orthogonal matching pursuit (OMP). Users are assigned into different clusters and the base station (BS) transmits superposed signals that share the same precoding vector. Moreover, both fixed number of users per cluster and dynamic number of users per cluster are investigated. We aim to jointly optimize the user clustering, service scheduling, and power allocation strategy, in maximizing the proportional fairness (PF) among the users and exploring the multiuser diversity and multiplexing gain. Since the formulated joint user clustering, scheduling and power allocation problem is a mixed integer non-convex optimization problem, we propose a twofold methodology. First, we apply a hybrid precoding and user clustering scheme, where the hybrid precoder is constructed by singular vector division (SVD) or minimum mean square error (MMSE). Then, with the obtained result, we approximate the proportional fairness power allocation problem by a sequence of Geometric Programming (GP) problems which are solved iteratively. The proposed scheme strikes a balance between the spectral efficiency and service fairness. Results show that the proposed MISO-NOMA scheme which is based on MMSE hybrid precoder and the proposed user scheduling and power allocation strategy under proportional fairness metric can outperform various conventional MISO schemes. Furthermore, our proposed dynamic number of users per cluster scheme outperforms the fixed scheme and can be considered as an upper bound in several aspects, including spectral efficiency and fairness

CHIP Represses Myocardin-Induced Smooth Muscle Cell Differentiation via Ubiquitin-Mediated Proteasomal Degradation▿

Myocardin, a coactivator of serum response factor (SRF), plays a critical role in the differentiation of vascular smooth muscle cells (SMCs). However, the molecular mechanisms regulating myocardin stability and activity are not well defined. Here we show that the E3 ligase C terminus of Hsc70-interacting protein (CHIP) represses myocardin-dependent SMC gene expression and transcriptional activity. CHIP interacts with and promotes myocardin ubiquitin-mediated degradation by the proteasome in vivo and in vitro. Furthermore, myocardin ubiquitination by CHIP requires its phosphorylation. Importantly, CHIP overexpression reduces the level of myocardin-dependent SMC contractile gene expression and diminishes arterial contractility ex vivo. These findings for the first time, to our knowledge, demonstrate that CHIP-promoted proteolysis of myocardin plays a key role in the physiological control of SMC phenotype and vessel tone, which may have an important implication for pathophysiological conditions such as atherosclerosis, hypertension, and Alzheimer's disease

Ultra-deep desulfurization via reactive adsorption on Ni/ZnO: The effect of ZnO particle size on the adsorption performance

The effect of ZnO particle size on the adsorptive desulfurization performance for Ni/ZnO (5 wt% NiO) adsorbent was investigated using thiophene as a sulfur containing compound in model gasoline with a fixed bed reactor. The Ni/ZnO adsorbents with different ZnO particle sizes (8, 12, 20, 30 nm) were prepared by an impregnation method and characterized by powder X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM) and transmission electron microscopy (TEM). It was found that the adsorption capacity of the Ni/ZnO adsorbent for thiophene significantly increased with the decrease of the ZnO particle sizes. Typically at a breakthrough sulfur level of 1 mg/L, sulfur capacity of Ni/ZnO (8 nm) from model gasoline (500 mg/L) is much higher than that of Ni/ZnO (30 nm) from 84 mg sulfur per gram adsorbent to nearly 0 mg sulfur per gram adsorbent. This higher desulfurization activity and sulfur capacity for Ni/ZnO with smaller ZnO particle sizes could be derived from higher Ni dispersion on ZnO and lower mass transfer limitations of sulfur to ZnO from Ni in H-2. (C) 2012 Elsevier BM. All rights reserved