• Title/Summary/Keyword: Mad2

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Inactivation of Mad2B Enhances Apoptosis in Human Cervical Cancer Cell Line upon Cisplatin-Induced DNA Damage

  • Ju Hwan Kim;Hak Rim Kim;Rajnikant Patel
    • Biomolecules & Therapeutics
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    • v.31 no.3
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    • pp.340-349
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    • 2023
  • Mad2B (Mad2L2), the human homolog of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares sequence similarity with the mitotic checkpoint protein Mad2A. Previous studies on Mad2B have concluded that it is a mitotic checkpoint protein that functions by inhibiting the anaphase-promoting complex/cyclosome (APC/C). Here, we demonstrate that Mad2B is activated in response to cisplatin-induced DNA damage. Mad2B co-localizes at nuclear foci with DNA damage markers, such as proliferating cell nuclear antigen and gamma histone H2AX (γ-H2AX), following cisplatin-induced DNA damage. However, unlike Mad2A, the binding of Mad2B to Cdc20 does not inhibit the activity of APC/C in vitro. In contrast to Mad2A, Mad2B does not localize to kinetochores or binds to Cdc20 in spindle assembly checkpoint-activated cells. Loss of the Mad2B protein leads to damaged nuclei following cisplatin-induced DNA damage. Mad2B/Rev7 depletion causes the accumulation of damaged nuclei, thereby accelerating apoptosis in human cancer cells in response to cisplatin-induced DNA damage. Therefore, our results suggest that Mad2B may be a critical modulator of DNA damage response.

Mad2B forms a complex with Cdc20, Cdc27, Rev3 and Rev1 in response to cisplatin-induced DNA damage

  • Ju Hwan Kim;Rajnikant Patel
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.5
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    • pp.427-436
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    • 2023
  • Mitotic arrest deficient 2 like 2 (Mad2L2, also known as Mad2B), the human homologue of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares high sequence homology with Mad2, the mitotic checkpoint protein. Previously, we demonstrated the involvement of Mad2B in the cisplatin-induced DNA damage response. In this study, we extend our findings to show that Mad2B is recruited to sites of DNA damage in human cancer cells in response to cisplatin treatment. We found that in undamaged cells, Mad2B exists in a complex with Polζ-Rev1 and the APC/C subunit Cdc27. Following cisplatin-induced DNA damage, we observed an increase in the recruitment of Mad2B and Cdc20 (the activators of the APC/C), to the complex. The involvement of Mad2B-Cdc20-APC/C during DNA damage has not been reported before and suggests that the APC/C is activated following cisplatin-induced DNA damage. Using an in vitro ubiquitination assay, our data confirmed Mad2B-dependent activation of APC/C in cisplatin-treated cells. Mad2B may act as an accelerator for APC/C activation during DNA damage response. Our data strongly suggest a role for Mad2B-APC/C-Cdc20 in the ubiquitination of proteins involved in the DNA damage response.

Functional Characterization of the Madlp, a Spindle Checkpoint Protein in Fission Yeast

  • Kim, In-Gyu;Rhee, Dong-Keun;Lee, Hee-Cheul;Lee, Joo;Kim, Hyong-Bai
    • Journal of Microbiology and Biotechnology
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    • v.15 no.4
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    • pp.694-700
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    • 2005
  • Defects in the mitotic spindle or in the attachment of chromosomes to the spindle are believed to release an activated form of spindle checkpoint complex that inhibits APC-dependent ubiquitination and subsequently arrests the cell cycle at metaphase. When the spindle assembly is disrupted, the fission yeast mitotic arrest deficient (mad) mutants fail to arrest and rapidly lose viability. To enhance our understanding of the molecular mechanisms for the pathway of checkpoint function, the functional characterizations of Mad 1 p from Schizosaccharomyces pombe involved in this process have been carried out. Yeast two-hybrid and various deletion analyses of S. pombe Mad1 p reveal that the C terminus of Mad1p is critical for the binding of Mad2p and maintenance of Mad 1 p-Mad2p interaction. In addition, it was found. that the Mad1p region (residues 206-356) is essential for Mad1p-other checkpoint components. Mad1p truncating this region is sufficient to bind Mad2p but abolishes the checkpoint function, indicating that the checkpoint function is necessary for interaction of Mad 1 p-other checkpoint components. The possible functions of S. pombe Mad1p at the cell cycle checkpoint are discussed.

Fast Block Matching Algorithm Using The Distribution of Mean Absolute Difference at The Search Region Overlapped with Neighbor Blocks and Subsampling (이웃 블록과 중첩된 탐색영역에서의 MAD 분포 및 부표본화를 이용한 고속 블록 정합)

  • 이법기;정원식;이경환;최정현;김경규;김덕규
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.24 no.8B
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    • pp.1506-1517
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    • 1999
  • In this paper, we propose two fast block matching algorithm using the distribution of mean absolute difference (MAD) at the search region overlapped with neighbor blocks and pixel subsapmling. The proposed methods use the lower and upper bound of MAD at the overlapped search region which is calculated from the MAD of neighbor block at that search position and MAD between the current block and neighbor block. In the first algorithm, we can reduce the computational complexity by executing the block matching operation at the only necessary search points. That points are selected using the lower bound of MAD. In the second algorithm, we use the statictical distribution of actual MAD which exists between the lower bound and upper bound of MAD. By using the statistical distribution of actual MAD, we can significantly reduce the computational complexity for motion estimation. after striking space key 2 times.

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MMAD Computation for Fast Diamond-Search Algorithm (고속 다이아몬드 탐색 알고리즘을 위한 MMAD 연산법)

  • 서은주;김동우;한재혁;안재형
    • Journal of Korea Multimedia Society
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    • v.4 no.5
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    • pp.406-413
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    • 2001
  • Ordinary high-speed block matching algorithms have a disadvantage that they need to get MAD (Mean Absolute Distance) as many as the number of search points due to comparing the MAD between the current frame's search block and the reference frame's search block. To solve such disadvantage of high-speed block matching algorithm, the proposed high-speed DS algorithm employs a MMAD calculation method using a specific characteristic that neighboring pixels have almost same values. In this thesis, we can get rid of unnecessary MAD calculation between the search point block by the new calculation method which uses the previously calculated MAD as the current search point and by breaking from the established MAD calculation method which calculates the MAD of a new search point by each search stage. Comparing with the established high-speed block matching algorithm, this new calculation's estimated movement error was shown as similar, and th total calculation amount decreased by $2FN^2Ep$.

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Delay in the Cell Cycle by a Single Unattached Kinetochore (방추사와 연결되지 않은 단 하나의 키네토코어가 세포분열의 속도를 늦추는 기전)

  • Kim, Taekyung
    • Journal of Life Science
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    • v.32 no.2
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    • pp.161-166
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    • 2022
  • Mitosis is a process in which a replicated genome is distributed to two daughter cells, and it is necessary for cell survival and organismal development. During mitosis, the spindle assembly checkpoint (SAC) ensures faithful chromosome segregation by monitoring the kinetochore attachment to the mitotic spindle. Although the SAC mechanism has been extensively studied over the last 30 years, the mechanism by which a single unattached kinetochore activates the SAC remains unclear. The key components of the SAC are Mad1, Mad2, Mad3 (BubR1 in higher eukaryotes), Bub1, Bub3, and Cdc20, which are all required for SAC activation. An essential step for SAC activation is the formation of the Mad2 - Cdc20 complex in the unattached kinetochore, which is kinetically disfavored. Although the mechanism by which Mad2 and Cdc20 are recruited to unattached kinetochores is well-known, it is not clear how they form a complex. Recently, a key mechanism for the formation of the Mad2 - Cdc20 complex has been identified, which is catalyzed by an unattached kinetochore. This supports the evidence that a single unattached kinetochore can activate the SAC signaling. Herein, we discuss the known key mechanism for SAC activation, review the recent studies on SAC, and conclude how their discoveries improved the understanding of mitosis.

MPEG Video Coding Using 2-Step MAD Motion Vector Search (2단계 MAD 움직임 탐색을 이용한 MPEG 동영상 부호화)

  • 이경환;류권열
    • Proceedings of the Korea Multimedia Society Conference
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    • 2001.06a
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    • pp.120-123
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    • 2001
  • MPEG 동영상 부호화 중 BMA를 이용한 움직임 탐색과정에서, 왜곡척도로 MAD를 사용하는데 이는 블록 내 모든 화소에 동일하게 적용되므로 구획화 현상 등을 일으켜 주관적인 화질을 떨어뜨리는 원인이 된다. 본 논문에서는 블록 내 화소를 경계 영역과 내부 영역으로 나누어 경계 영역에 대한 MAD를 먼저 구하고, 문턱치를 비교하여 인터블록과 인트라 블록으로 구분하고 인터로 분류된 블록에 대해서만 내부 영역의 MAD를 구하여 최종 보상블록을 결정함으로써 화질을 개선하고 계산량을 줄일 수 있었다.

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Treatment Outcomes of Mandibular Advancement Devices in Mild, Moderate, and Severe Obstructive Sleep Apnea: A Preliminary Study

  • Hye Kyoung Kim;Mee Eun Kim
    • Journal of Oral Medicine and Pain
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    • v.48 no.3
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    • pp.96-105
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    • 2023
  • Purpose: Mandibular advancement devices (MAD) are known to be insufficiently effective in all patients with obstructive sleep apnea (OSA). This study aimed to compare the treatment outcomes of MAD therapy according to OSA severity and to investigate the risk factors for the lack of response to MAD therapy. Methods: A total of 29 patients diagnosed with OSA received an adjustable two-piece MAD treatment. Sleep parameters measured with the home sleep apnea test device, including apnea-hypopnea index (AHI) and oxygen saturation (SpO2), and daytime sleepiness using the Epworth Sleepiness Scale (ESS) were retrospectively assessed both before and after the MAD treatment. Results: The patients were classified into three groups according to AHI severity: mild (n=16, AHI<15), moderate (n=6, 15≤AHI<30), and severe OSA (n=7, AHI≥30). MAD therapy significantly improved the sleep parameters (p<0.001 for AHI and p=0.004 for minimum SpO2) and daytime sleepiness (p<0.001 for ESS). Furthermore, successful outcomes (reduction in AHI>50% and AHI<10 events/h) were achieved in 83.3% and 71.4% of moderate and severe OSA cases, respectively. Of 13 patients with moderate and severe OSA, 10 were classified as responders and 3 as non-responders. The non-responders had significantly lower baseline value of SpO2 (p=0.049 for average SpO2 and p=0.007 for minimum SpO2) and higher baseline AHI (p=0.049) than the responders. Conclusions: The results of the present study suggest that MAD is effective in the majority of patients with OSA of varying severities. The success of MAD therapy does not seem to depend solely on AHI severity. In addition to AHI, minimum SpO2 may be a prognostic measure of the efficacy of MAD treatment in clinical dental practice.

Treatment Outcomes of Mandibular Advancement Devices between Rapid-Eye-Movement (REM)-Related and Not-REM-Related OSA Patients

  • Oh, Jae-Tak;Jang, Ji-Hee;Chung, Jin-Woo
    • Journal of Oral Medicine and Pain
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    • v.41 no.2
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    • pp.54-60
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    • 2016
  • Purpose: Mandibular advancement devices (MAD) are used effectively and widely for the treatment of obstructive sleep apnea (OSA) and rapid-eye-movement (REM) dependency of the patients can affect the treatment outcome of OSA. The aim of this study was to compare treatment outcomes of MAD between REM-related and not-REM-related OSA patients. Methods: Fifty-six consecutive patients with OSA who received MAD therapy were evaluated using full night polysomnography before and after insertion of the MADs. The patients were divided into REM-related (REM apnea-hypopnea index [AHI] at least two times higher than their non-REM AHI) and not-REM-related (REM AHI less than two times higher than their non-REM AHI) OSA groups. Results: MAD is used for the treatment of OSA effectively. In respect of AHI, MAD therapy were effective both in REM-related OSA and not-REM-related OSA, but MAD therapy was more effective in not-REM-related OSA than REM-related OSA in overall sleep and non-REM sleep. $SpO_2$ saturations were improved after MAD therapy, but were not different between two groups. Epworth sleepiness scale scores were not improved after MAD therapy. Percentage of REM sleep was increased after MAD therapy but was not different between two groups. Conclusions: MAD therapy was more effective in not-REM-related OSA than REM-related OSA and REM dependency can be a predictive factor of treatment outcome of oral appliance for OSA patients.

Unsupervised Change Detection for Very High-spatial Resolution Satellite Imagery by Using Object-based IR-MAD Algorithm (객체 기반의 IR-MAD 기법을 활용한 고해상도 위성영상의 무감독 변화탐지)

  • Jaewan, Choi
    • Journal of the Korean Society of Surveying, Geodesy, Photogrammetry and Cartography
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    • v.33 no.4
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    • pp.297-304
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    • 2015
  • The change detection algorithms, based on remotely sensed satellite imagery, can be applied to various applications, such as the hazard/disaster analysis and the land monitoring. However, unchanged areas sometimes detected as the changed areas due to various errors in relief displacements and noise pixels, included in the original multi-temporal dataset at the application of unsupervised change detection algorithm. In this research, the object-based changed detection for the high-spatial resolution satellite images is applied by using the IR-MAD (Iteratively Reweighted- Multivariate Alteration Detection), which is one of those representative change detection algorithms. In additionally, we tried to increase the accuracy of change detection results with using the additional information, based on the cross-sharpening method. In the experiment, we used the KOMPSAT-2 satellite sensor, and resulted in the object-based IR-MAD algorithm, representing higher changed detection accuracy than that by the pixel-based IR-MAD. Also, the object-based IR-MAD, focused on cross-sharpened images, increased in accuracy of changed detection, compared to the original object-based IR-MAD. Through these experiments, we could conclude that the land monitoring and the change detection with the high-spatial-resolution satellite imagery can be accomplished efficiency by using the object-based IR-MAD algorithm.