• Title/Summary/Keyword: Cellular instability

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PIG3 Regulates p53 Stability by Suppressing Its MDM2-Mediated Ubiquitination

  • Jin, Min;Park, Seon-Joo;Kim, Seok Won;Kim, Hye Rim;Hyun, Jin Won;Lee, Jung-Hee
    • Biomolecules & Therapeutics
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    • v.25 no.4
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    • pp.396-403
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    • 2017
  • Under normal, non-stressed conditions, intracellular p53 is continually ubiquitinated by MDM2 and targeted for degradation. However, in response to severe genotoxic stress, p53 protein levels are markedly increased and apoptotic cell death is triggered. Inhibiting the ubiquitination of p53 under conditions where DNA damage has occurred is therefore crucial for preventing the development of cancer, because if cells with severely damaged genomes are not removed from the population, uncontrolled growth can result. However, questions remain about the cellular mechanisms underlying the regulation of p53 stability. In this study, we show that p53-inducible gene 3 (PIG3), which is a transcriptional target of p53, regulates p53 stability. Overexpression of PIG3 stabilized both endogenous and transfected wild-type p53, whereas a knockdown of PIG3 lead to a reduction in both endogenous and UV-induced p53 levels in p53-proficient human cancer cells. Using both in vivo and in vitro ubiquitination assays, we found that PIG3 suppressed both ubiquitination- and MDM2-dependent proteasomal degradation of p53. Notably, we demonstrate that PIG3 interacts directly with MDM2 and promoted MDM2 ubiquitination. Moreover, elimination of endogenous PIG3 in p53-proficient HCT116 cells decreased p53 phosphorylation in response to UV irradiation. These results suggest an important role for PIG3 in regulating intracellular p53 levels through the inhibition of p53 ubiquitination.

A Structural Behavior of the Propane/Air Premixed Flame Interacting with an Ultrasonic Standing-wave (정상초음파가 개재하는 프로판/공기 예혼합화염의 구조 거동)

  • Lee, Sang-Shin;Seo, Hang-Seok;Kim, Jeong-Soo;Lee, Do-Hyung
    • Proceedings of the Korean Society of Propulsion Engineers Conference
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    • 2012.05a
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    • pp.294-299
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    • 2012
  • An investigation into the influence of ultrasonic standing wave on the structural behavior of propane/air premixed flame has been made to get a clue to the combustion reaction acceleration and combustion instability, as well. Visualization technique utilizing the Schlieren method was employed for the observation of structural variation of the premixed flame. The flame shape and propagation velocity were measured according to the variation of equivalence ratio. It was found that the standing wave distorted the flame front and expedited a transition to the flame with turbulent nature.

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How Chromosome Mis-Segregation Leads to Cancer: Lessons from BubR1 Mouse Models

  • Lee, Hyunsook
    • Molecules and Cells
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    • v.37 no.10
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    • pp.713-718
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    • 2014
  • Alteration in chromosome numbers and structures instigate and foster massive genetic instability. As Boveri has seen a hundred years ago (Boveri, 1914; 2008), aneuploidy is hall-mark of many cancers. However, whether aneuploidy is the cause or the result of cancer is still at debate. The molecular mechanism behind aneuploidy includes the chromosome mis-segregation in mitosis by the compromise of spindle assembly checkpoint (SAC). SAC is an elaborate network of proteins, which monitor that all chromosomes are bipolarly attached with the spindles. Therefore, the weakening of the SAC is the major reason for chromosome number instability, while complete compromise of SAC results in detrimental death, exemplified in natural abortion in embryonic stage. Here, I will review on the recent progress on the understanding of chromosome missegregation and cancer, based on the comparison of different mouse models of BubR1, the core component of SAC.

Potential roles of reactive oxygen species derived from chemical substances involved in cancer development in the female reproductive system

  • Kim, Soo-Min;Hwang, Kyung-A;Choi, Kyung-Chul
    • BMB Reports
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    • v.51 no.11
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    • pp.557-562
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    • 2018
  • Reactive oxygen species (ROS) are major sources of cellular oxidative stress. Specifically, cancer cells harbor genetic alterations that promote a continuous and elevated production of ROS. While such oxidative stress conditions could be harmful to normal cells, they facilitate cancer cell growth in multiple ways by causing DNA damage and genomic instability, and ultimately by reprogramming cancer cell metabolism. This review provides up to date findings regarding the roles of ROS generation induced by diverse biological molecules and chemicals in representative women's cancer. Specifically, we describe the cellular signaling pathways that regulate direct or indirect interactions between ROS homeostasis and metabolism within female genital cancer cells.

Effects of propane substitution for safety improvement of hydrogen-air flame (수소-공기 화염의 안전성 향상을 위한 프로판 첨가 효과)

  • Kwon, Oh-Chae
    • Journal of Hydrogen and New Energy
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    • v.15 no.1
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    • pp.12-22
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    • 2004
  • In order to evaluate the potential of partial hydrocarbon substitution to improve the safety of hydrogen use in general and the performance of internal combustion engines in particular, the outward propagation and development of surface cellular instability of spark-ignited spherical premixed flames of mixtures of hydrogen, hydrocarbon, and air were experimentally studied at NTP (normal temperature and pressure) condition in a constant-pressure combustion chamber. With propane being the substituent, the laminar burning velocities, the Markstein lengths, and the propensity of cell formation were experimentally determined, while the laminar burning velocities and the associated flame thicknesses were computed using a recent kinetic mechanism. Results show substantial reduction of laminar burning velocities with propane substitution, and support the potential of propane as a suppressant of both diffusional-thermal and hydrodynamic cellular instabilities in hydrogen-air flames.

Pleiotropic Effects of Caffeine Leading to Chromosome Instability and Cytotoxicity in Eukaryotic Microorganisms

  • Chung, Woo-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.31 no.2
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    • pp.171-180
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    • 2021
  • Caffeine, a methylxanthine analog of purine bases, is a compound that is largely consumed in beverages and medications for psychoactive and diuretic effects and plays many beneficial roles in neuronal stimulation and enhancement of anti-tumor immune responses by blocking adenosine receptors in higher organisms. In single-cell eukaryotes, however, caffeine somehow impairs cellular fitness by compromising cell wall integrity, inhibiting target of rapamycin (TOR) signaling and growth, and overriding cell cycle arrest caused by DNA damage. Among its multiple inhibitory targets, caffeine specifically interacts with phosphatidylinositol 3-kinase (PI3K)-related kinases causing radiosensitization and cytotoxicity via specialized intermediate molecules. Caffeine potentiates the lethality of cells in conjunction with several other stressors such as oxidants, irradiation, and various toxic compounds through largely unknown mechanisms. In this review, recent findings on caffeine effects and cellular detoxification schemes are highlighted and discussed with an emphasis on the inhibitory interactions between caffeine and its multiple targets in eukaryotic microorganisms such as budding and fission yeasts.

New Cellular Neural Networks Template for Image Halftoning based on Bayesian Rough Sets

  • Elsayed Radwan;Basem Y. Alkazemi;Ahmed I. Sharaf
    • International Journal of Computer Science & Network Security
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    • v.23 no.4
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    • pp.85-94
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    • 2023
  • Image halftoning is a technique for varying grayscale images into two-tone binary images. Unfortunately, the static representation of an image-half toning, wherever each pixel intensity is combined by its local neighbors only, causes missing subjective problem. Also, the existing noise causes an instability criterion. In this paper an image half-toning is represented as a dynamical system for recognizing the global representation. Also, noise is reduced based on a probabilistic model. Since image half-toning is considered as 2-D matrix with a full connected pass, this structure is recognized by the dynamical system of Cellular Neural Networks (CNNs) which is defined by its template. Bayesian Rough Sets is used in exploiting the ideal CNNs construction that synthesis its dynamic. Also, Bayesian rough sets contribute to enhance the quality of the halftone image by removing noise and discovering the effective parameters in the CNNs template. The novelty of this method lies in finding a probabilistic based technique to discover the term of CNNs template and define new learning rules for CNNs internal work. A numerical experiment is conducted on image half-toning corrupted by Gaussian noise.

Post-Translational Regulation of the RSF1 Chromatin Remodeler under DNA Damage

  • Min, Sunwoo;Choi, Yong Won;Yun, Hansol;Jo, Sujin;Ji, Jae-Hoon;Cho, Hyeseong
    • Molecules and Cells
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    • v.41 no.2
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    • pp.127-133
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    • 2018
  • Chromatin remodeling factors are involved in many cellular processes such as transcription, replication, and DNA damage response by regulating chromatin structure. As one of chromatin remodeling factors, remodeling and spacing factor 1 (RSF1) is recruited at double strand break (DSB) sites and regulates ataxia telangiectasia mutated (ATM) -dependent checkpoint pathway upon DNA damage for the efficient repair. RSF1 is overexpressed in a variety of cancers, but regulation of RSF1 levels remains largely unknown. Here, we showed that protein levels of RSF1 chromatin remodeler are temporally upregulated in response to different DNA damage agents without changing the RSF1 mRNA level. In the absence of SNF2h, a binding partner of RSF1, the RSF1 protein level was significantly diminished. Intriguingly, the level of RSF1-3SA mutant lacking ATM-mediated phosphorylation sites significantly increased, and upregulation of RSF1 levels under DNA damage was not observed in cells overexpressing ATM kinase. Furthermore, failure in the regulation of RSF1 level caused a significant reduction in DNA repair, whereas reconstitution of RSF1, but not of RSF1-3SA mutants, restored DSB repair. Our findings reveal that temporal regulation of RSF1 levels at its post-translational modification by SNF2h and ATM is essential for efficient DNA repair.

Cell-type-specific Gene Expression Patterns in Human Carcinoma Cells followed by Irradiation (방사선에 의한 암세포주 특이적 유전자 발현 양상)

  • Park Ji-Yoon;Kim Jin-Kyu;Chai Young Gyu
    • Korean Journal of Environmental Biology
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    • v.23 no.2 s.58
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    • pp.152-156
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    • 2005
  • Ionizing radiation is a well- known therapy factor for human carcinoma cells. Genotoxic stress mediates cell cycle control, transcription and cellular signaling. In this work, we have used a microarray hybridization approach to characterize the cell type-specific transcriptional response of human carcinoma MCF-7 and HeLa cell line to $\gamma-radiation$, such as 4Gy 4hr. We found that exposure to $\gamma-ray$ alters by at least a $log_2$ factor of 1.0 the expression of known genes. Of the 27 genes affected by irradiation, 11 are down- regulated in MCF-7 cells and 2 genes induced by radiation,15 are repressed in HeLa cells. Many genes were involved in known damage- response pathways for cell cycling, transcription factor and cellular signaling response. However, in MCF-7 cells, we observed gene expression pattern in chromatin, apoptosis, stress, differentiation, cytokine, metabolism, ribosome and calcium. In HeLa cells, it showed clearly the expression changes in adhesion and migration, lysosome, brain, genome instability and translation. These insights reveal new therapy directions for studying the human carcinoma cell response to radiation.

Evaluation of MT1XT20 Single Quasi-Monomorphic Mononucleotide Marker for Characterizing Microsatellite Instability in Persian Lynch Syndrome Patients

  • Farahani, Najmeh;Nikpour, Parvaneh;Emami, Mohammad Hassan;Hashemzadeh, Morteza;Zeinalian, Mehrdad;Shariatpanahi, Seyed Shervin;Salehi, Rasoul
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.9
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    • pp.4259-4265
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    • 2016
  • Background: Colorectal malignancies with high microsatellite instability (MSI-H), either hereditary (Lynch syndrome) or sporadic, demonstrate better prognosis and altered response to 5FU chemotherapy. It is now recommended to perform MSI testing for all new cases of colorectal cancer regardless of being categorized as hereditary or sporadic. For MSI detection, immunohistochemistry or PCR-based protocols using a cohort of various sets of STR markers are recommended. Here we aimed to evaluate a simplified protocol using just a single STR marker, MT1XT20 mononucleotide repeat, for detection of MSI in Lynch syndrome patients. A Promega five-marker MSI testing panel and immunohistochemistry (IHC) were used as the gold standard in conjunction with MT1XT20. Materials and Methods: Colorectal patients with a positive history of familial cancers were selected by evaluating medical records. Based on Amsterdam II criteria for Lynch syndrome 20 families were short listed. DNA was extracted from formalin fixed paraffin embedded tumour and adjacent normal tissues resected from the index case in each family. Extracted DNA was subjected to MT1XT20 mononucleotide marker analysis and assessment with a commercially available five marker MSI testing kit (Promega, USA). IHC also was performed on tissue sections and the results were compared with PCR based data. Results: Eight (40%), seven (35%) and five (25%) cases were MSI positive using with the Promega kit, IHC and MT1XT20, respectively. Among the markers included in Promega kit, BAT26 marker showed instability in all 8 samples. NR24 and NR21 markers showed instability in 7 (87.5%), and BAT25 and MONO 27 in 6 (75%) and 5 (62.5%). Conclusions: Although MT1XT20 was earlier reported as a valid standalone marker for MSI testing in CRC patients, we could not verify this in our Iranian patients. Instead BAT26 among the markers included in Promega MSI testing kit showed instability in all 8 MSI-H CRC samples. Therefore, it seems BAT26 could act well as a single marker for MSI testing in Iranian CRC patients.