• Title, Summary, Keyword: RIP

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Regulation of RIP3 protein stability by PELI1-mediated proteasome-dependent degradation

  • Park, Han-Hee;Morgan, Michael J.;Kang, Ho Chul;Kim, You-Sun
    • BMB Reports
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    • v.51 no.10
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    • pp.484-485
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    • 2018
  • Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is a serine-threonine kinase largely essential for necroptotic cell death; it also plays a role in some inflammatory diseases. High levels of RIP3 are likely sufficient to activate necroptotic and inflammatory pathways downstream of RIP3 in the absence of an upstream stimulus. For example, we have previously detected high levels or RIP3 in the skin of Toxic Epidermal Necrolysis patients; this correlates with increased phosphorylation of MLKL found in these patients. We have long surmised that there are molecular mechanisms to prevent anomalous activity of the RIP3 protein, and so prevent undesirable cell death and inflammatory effects when inappropriately activated. Recent discovery that Carboxyl terminus of Hsp 70-Interacting Protein (CHIP) could mediate ubiquitylation- and lysosome-dependent RIP3 degradation provides a potential protein that has this capacity. However, while screening for RIP3-binding proteins, we discovered that pellino E3 ubiquitin protein ligase 1 (PELI1) also interacts directly with RIP3 protein; further investigation in this study revealed that PELI1 also targets RIP3 for proteasome-dependent degradation. Interestingly, unlike CHIP, which targets RIP3 more generally, PELI1 preferentially targets kinase active RIP3 that has been phosphorylated on T182, subsequently leading to RIP3 degradation.

Species-specific variation of RPA-interacting protein (RIP) splice isoforms

  • Kim, Kwang-Soo;Lee, Eun-Ju;Lee, Seung-Hoon;Seo, Tae-Gun;Jang, Ik-Soon;Park, Jun-Soo;Lee, Je-Ho
    • BMB Reports
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    • v.42 no.1
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    • pp.22-27
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    • 2009
  • Replication Protein A (RPA) is a single stranded DNA-binding protein involved in DNA metabolic activities such as replication, repair, and recombination. RPA-Interacting Protein $\alpha$ ($RIP{\alpha}$) was originally identified as a nuclear transporter of RPA in Xenopus. The human $RIP{\alpha}$ gene encodes several splice isoforms, of which $hRIP{\alpha}$ and $hRIP{\beta}$ are the major translation products in vivo. However, limited information is available about the alternative splicing of $RIP{\alpha}$ in eukaryotes, apart from that in humans. In this study, we examined the alternative splicing of RIP{\alpha} in the Drosophila, Xenopus, and mouse system. We showed that the number of splice isoforms of RIP{\alpha} was species-specific, and displayed a tendency to increase in higher eukaryotes. Moreover, a mouse ortholog of $hRIP{\alpha}$, $mRIP{\beta}2$, was not SUMOylated, in contrast to $hRIP{\alpha}$. Based on these results, we suggest that the $RIP{\alpha}$ gene gains more splice isoforms and additional modifications after molecular evolution.

Nearshore Current Pattern and Rip Current Occurrence at Jungmun Beach, Jeju by Numerical Computation

  • An, Seung-Hyun;Kim, Nam-Hyeong
    • Journal of Navigation and Port Research
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    • v.41 no.2
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    • pp.55-62
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    • 2017
  • A nearshore current or a wave-induced current is an important phenomenon in a nearshore zone, which is composed of longshore, cross-shore, and rip currents. The nearshore current is closely related to the occurrence of coastal accidents by beachgoers. A considerable number of coastal accidents by beachgoers involving the rip current have been reported at Jungmun Beach. However, in studies and observations of the nearshore current of Jungmun Beach, understanding of the rip current pattern remains unclear. In this study, a scientific approach is taken to understand the nearshore current and the rip current patterns at Jungmun Beach by numerical computation for year of 2015. From results of numerical computation, the occurrence and spatial characteristics of the rip current, and the similarities between the rip current and incident wave conditions are analyzed. The primary results of this study reveal that the rip currents are frequently generated at Jungmun Beach, especially in the western parts of the beach, and that the rip currents often occur with a wave breaking height of around 0.5 ~ 0.7 m, a wave period of around 6 ~ 8 seconds, and a breaking angle of around 0 ~ 15 degrees.

Development of a Simplified Statistical Methodology for Nuclear Fuel Rod Internal Pressure Calculation

  • Kim, Kyu-Tae;Kim, Oh-Hwan
    • Nuclear Engineering and Technology
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    • v.31 no.3
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    • pp.257-266
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    • 1999
  • A simplified statistical methodology is developed in order to both reduce over-conservatism of deterministic methodologies employed for PWR fuel rod internal pressure (RIP) calculation and simplify the complicated calculation procedure of the widely used statistical methodology which employs the response surface method and Monte Carlo simulation. The simplified statistical methodology employs the system moment method with a deterministic approach in determining the maximum variance of RIP The maximum RIP variance is determined with the square sum of each maximum value of a mean RIP value times a RIP sensitivity factor for all input variables considered. This approach makes this simplified statistical methodology much more efficient in the routine reload core design analysis since it eliminates the numerous calculations required for the power history-dependent RIP variance determination. This simplified statistical methodology is shown to be more conservative in generating RIP distribution than the widely used statistical methodology. Comparison of the significances of each input variable to RIP indicates that fission gas release model is the most significant input variable.

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Rip-off Failure Mechanism of Reinforced Concrete Beams Strengthened with CFRP Plate (CFRP로 성능향상된 철근콘크리트 보의 Rip-off 파괴메커니즘 고찰)

  • Sim Jong-Sung;Moon Do-Young;Park Cheol-Woo;Park Sung-Jae;Choi Kwang-Min
    • Journal of the Korea Concrete Institute
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    • v.17 no.6
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    • pp.993-1000
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    • 2005
  • Various types of FRP materials have been applied for structural strengthening of RC beams in various forms. When CFRP plates are used, a premature failure used to occur before enough strengthening effect appears. This is primarily due to the rip-off of CFRP Plate attached on RC beams. Despite of numerous studies on the rip-off failure of externally strengthened RC beams, its failure mechanism is not definitely clarified yet. Investigations from literatures have shown that the rip-off failure is dependant on the vertical and shear stresses at the level of main reinforcements in RC beams. This study suggests an analytical model to Investigate the rip-off failure load based on the stress states at the level of main reinforcements. The proposed model is relatively simple and produces very comparable results to the test data. It is believed that the proposed model can be successfully used to provide more information on the rip-off failure mechanisms and its prevention.

HS-1371, a novel kinase inhibitor of RIP3-mediated necroptosis

  • Park, Han-Hee;Park, Se-Yeon;Mah, Shinmee;Park, Jung-Hee;Hong, Soon-Sun;Hong, Sungwoo;Kim, You-Sun
    • Experimental and Molecular Medicine
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    • v.50 no.9
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    • pp.16.1-16.15
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    • 2018
  • Necroptosis is a type of programmed cell death that usually occurs under apoptosis-deficient conditions. Receptor-interacting protein kinase-3 (RIP3, or RIPK3) is a central player in necroptosis, and its kinase activity is essential for downstream necroptotic signaling events. Since RIP3 kinase activity has been associated with various diseases, the development of specific RIP3 inhibitors is an attractive strategy for therapeutic application. In this study, we identified a potent RIP3 inhibitor, HS-1371, by the extensive screening of chemical libraries focused on kinases. HS-1371 directly binds to RIP3 in an ATP-competitive and time-independent manner, providing a mechanism of action. Moreover, the compound inhibited TNF-induced necroptosis but did not inhibit TNF-induced apoptosis, indicating that this novel inhibitor has a specific inhibitory effect on RIP3-mediated necroptosis via the suppression of RIP3 kinase activity. Our results suggest that HS-1371 could serve as a potential preventive or therapeutic agent for diseases involving RIP3 hyperactivation.

Formulation and Cytotoxicity of Ribosome-Inactivating Protein Mirabilis Jalapa L. Nanoparticles Using Alginate-Low Viscosity Chitosan Conjugated with Anti-Epcam Antibodies in the T47D Breast Cancer Cell Line

  • Wicaksono, Psycha Anindya;Sismindari, Sismindari;Martien, Ronny;Ismail, Hilda
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.2277-2284
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    • 2016
  • Ribosome-inactivating protein (RIP) from Mirabilis jalapa L. leaves has cytotoxic effects on breast cancer cell lines but is less toxic towards normal cells. However, it can easily be degraded after administration so it needs to be formulated into nanoparticles to increase its resistance to enzymatic degradation. The objectives of this study were to develop a protein extract of M. jalapa L. leaves (RIP-MJ) incorporated into nanoparticles conjugated with Anti-EpCAM antibodies, and to determine its cytotoxicity and selectivity in the T47D breast cancer cell line. RIP-MJ was extracted from red-flowered M. jalapa L. leaves. Nanoparticles were formulated based on polyelectrolyte complexation using low viscosity chitosan and alginate, then chemically conjugated with anti-EpCAM antibody using EDAC based on carbodiimide reaction. RIP-MJ nanoparticles were characterised for the particle size, polydispersity index, zeta potential, particle morphology, and entrapment efficiency. The cytotoxicity of RIP-MJ nanoparticles against T47D and Vero cells was then determined with MTT assay. The optimal formula of RIP-MJ nanoparticles was obtained at the concentration of RIP-MJ, low viscosity chitosan and alginate respectively 0.05%, 1%, and 0.4% (m/v). RIP-MJ nanoparticles are hexagonal with high entrapment efficiency of 98.6%, average size of 130.7 nm, polydispersity index of 0.380 and zeta potential +26.33 mV. The $IC_{50}$ values of both anti-EpCAM-conjugated and non-conjugated RIP-MJ nanoparticles for T47D cells (13.3 and $14.9{\mu}g/mL$) were lower than for Vero cells (27.8 and $33.6{\mu}g/mL$). The $IC_{50}$ values of conjugated and non-conjugated RIP-MJ for both cells were much lower than $IC_{50}$ values of non-formulated RIP-MJ (>$500{\mu}g/mL$).

REFLEXIVE PROPERTY ON IDEMPOTENTS

  • Kwak, Tai Keun;Lee, Yang
    • Bulletin of the Korean Mathematical Society
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    • v.50 no.6
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    • pp.1957-1972
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    • 2013
  • The reflexive property for ideals was introduced by Mason and has important roles in noncommutative ring theory. In this note we study the structure of idempotents satisfying the reflexive property and introduce reflexive-idempotents-property (simply, RIP) as a generalization. It is proved that the RIP can go up to polynomial rings, power series rings, and Dorroh extensions. The structure of non-Abelian RIP rings of minimal order (with or without identity) is completely investigated.

Connections Between Various Trigger Factors and the RIP1/RIP3 Signaling Pathway Involved in Necroptosis

  • Zhang, Yuan-Yuan;Liu, Hao
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7069-7074
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    • 2013
  • Programmed cell death is a basic cellular process that is critical to maintaining tissue homeostasis. In contrast to apoptosis, necrosis was previously regarded as an unregulated and uncontrollable process. However, as research has progressed, necrosis, also known as necroptosis or programmed necrosis, is drawing increasing attention, not least becasu of its possible impications for cancer research. Necroptosis exhibits a unique signaling pathway that requires the involvement of receptor interaction protein kinases 1 and 3 (RIP1 and RIP3), mixed lineage kinase domain-like (MLKL), and phosphoglycerate mutase 5 (PGAM5) and can be specifically inhibited by necrostatins. Not only does necroptosis serve as a backup cell death program when apoptosis is inhibited, but it is now recognized to play a pivotal role in regulating various physiological processes and the pathogenesis of a variety of human diseases such as ischemic brain injury, immune system disorders and cancer. The control of necroptosis by various defined trigger factors and signaling pathways now offers the opportunity to target this cellular process for therapeutic purposes. The purpose of this paper is to review current findings concerning the connections between various trigger factors and the RIP1/RIP3 signaling pathway as it relates to necroptosis.

Study of Rip Current Warning Index Function according to Real-time Observations at Haeundae Beach in 2012 (2012년 해운대 해수욕장의 실시간 관측정보에 따른 이안류 경보지수 함수 연구)

  • Choi, Junwoo
    • Journal of The Korean Society of Civil Engineers
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    • v.34 no.4
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    • pp.1191-1201
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    • 2014
  • The rip current warning index function, which estimates the likelihood of dangerous rip current in the real-time rip current warning system operating to help mitigate against rip current accidents at Haeundae beach, was studied. The rip current warning index evaluated as a function of various real-time observations was developed based on Choi et al. (2013b). This study shows a version of rip current warning index improved by including the effect of wave direction and spreadings of frequency-directional spectrum on rip current likelihood. The wave and tidal observations in 2012 at Haeundae coast were applied to the rip current index function, and its performances at several real events found based on CCTV images were presented and analyzed.