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A converged ubiquitin-proteasome pathway for the degradation of TOC and TOM tail-anchored receptors

Journal of Integrative Plant Biology 2024年第5期66卷 1007-1023页

作者： Meijing Yang Shuai Chen Shey-Li Lim Lang Yang Jia Yi Zhong koon Chuen Chan Zhizhu Zhao Kam-Bo Wong Junqi Wang boon Leong Lim School of Biological Sciences University of Hong KongPokfulam 999077Hong KongChina Department of Biology Southern University of Science and TechnologyShenzhen 518055China School of Biomedical Engineering Shenzhen UniversityShenzhen 518060China School of Life Sciences The Chinese Universityof Hong KongShatin 999077HongKongChina State Key Laboratory of Agrobiotechnology The Chinese University of Hong KongShatin 999077Hong KongChina HKU Shenzhen Institute of Research and Innovation Shenzhen 518052China

In plants,thousands of nucleus-encoded proteins translated in the cytosol are sorted to chloroplasts and mitochondria by binding to specific receptors of the TOC(translocon on the outer chloroplast membrane)and the TOM(translocon on the outer mitochondrial membrane)complexes for import into those *** degradation pathways for these receptors are ***,we discovered a converged ubiquitin-proteasome pathway for the degradation of Arabidopsis thaliana TOC and TOM tail-anchored *** receptors are ubiquitinated by E3 ligase(s)and pulled from the outer membranes by the AAA+adenosine triphosphatase CDC48,after which a previously uncharacterized cytosolic protein,transmembrane domain(TMD)-binding protein for tail-anchored outer membrane proteins(TTOP),binds to the exposed TMDs at the C termini of the receptors and CDC48,and delivers these complexes to the 26S proteasome.

关键词： 26S proteasome CDC48 SP1 TOC TOM ubiquitination

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Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma:the PLANET study

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National Science Review 2022年第3期9卷 96-109页

作者： Weiwei Zhai Hannah Lai Neslihan Arife Kaya Jianbin Chen Hechuan Yang Bingxin Lu Jia Qi Lim Siming Ma Sin Chi Chew Khi Pin Chua Jacob Josiah Santiago Alvarez Pauline Jieqi Chen Mei Mei Chang Lingyan Wu Brian K.P.Goh Alexander Yaw-Fui Chung Chung Yip Chan Peng Chung Cheow Ser Yee Lee Juinn Huar Kam Alfred Wei-Chieh Kow Iyer Shridhar Ganpathi Rawisak Chanwat Jidapa Thammasiri boon koon yoong Diana Bee-Lan Ong Vanessa H.de Villa Rouchelle D.Dela Cruz Tracy Jiezhen Loh Wei Keat Wan Zeng Zeng Anders Jacobsen Skanderup Yin Huei Pang Krishnakumar Madhavan Tony Kiat-Hon Lim Glenn Bonney Wei Qiang Leow Valerie Chew Yock Young Dan Wai Leong Tam Han Chong Toh Roger Sik-Yin Foo Pierce Kah-Hoe Chow Genome Institute of Singapore Agency for Science Technology and Research Key Laboratory of Zoological Systematics and Evolution Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences School of Biological Sciences Nanyang Technological University Division of Biosciences Faculty of Life Sciences Division of Surgery and Surgical Oncology National Cancer Centre Department of Hepato-Pancreato-Biliary and Transplant Surgery Singapore General Hospital Division of Hepatobiliary and Pancreatic Surgery Department of Surgery University Surgical Cluster National University Health System Hepato-Pancreato-Biliary Surgery Unit Department of Surgery National Cancer Institute Division of Pathology National Cancer Institute Department of Surgery Faculty of Medicine University of Malaya Department of Surgery and Center for Liver Disease Management and Transplantation The Medical City 13. Department of Laboratories The Medical City Department of Pathology Singapore General Hospital Institute for Infocomm Research ASTAR Department of Pathology National University Health System Translational Immunology Institute (TII) Sing Health Duke-NUS Academic Medical Centre Division of Gastroenterology and Hepatology University Medicine Cluster National University Hospital Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Cancer Science Institute of Singapore National University of Singapore Division of Medical Oncology National Cancer Center Singapore Cardiovascular Research Institute National University of Singapore National University Healthcare System Singhealth-Duke-NUS Academic Surgery Program Duke-NUS Graduate Medical School Institute of Molecular and Cell Biology Agency for Science Technology and Research

Intra-tumor heterogeneity(ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic(transcriptomic and immune)heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma(HCC)with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients(331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage Ⅱ patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

关键词： NADH oxidase H2O2 production oxidative phosphorylation

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Survival analysis of cholangiocarcinoma:A 10-year experience in Malaysia

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World Journal of Gastroenterology 2012年第5期18卷 458-465页

作者： Ahmad Ramzi Yusoff Mohd Muzammil Abdul Razak yoong boon koon R Vijeyasingam Siti Zuraidah Mahmud Faculty of Medicine Universiti Teknologi MARASg.Buloh Campus47000 Sg.BulohSelangorMalaysia Department of Surgery University Malaya Medical Centre59100 Kuala LumpurMalaysia Institute for Medical Research Jalan Pahang50588 Kuala LumpurMalaysia

AIM:To investigate the clinical features and survival of patients treated for cholangiocarcinoma in our institution and to analyze the factors affecting their ***:This retrospective cohort study assessed patients diagnosed with cholangiocarcinoma between January 1997 and December 2007 at the University Malaya Medical Centre in *** clinical data and associated outcomes were collected using a structured ***:Of the 69 patients diagnosed with cholangiocarcinoma,38 (55%) were male;mean patient age was 61 *** patients (17%) had intrahepatic,38 (55%) had perihilar and 19 (28%) had distal *** 12 patients underwent curative surgery,including seven R0 *** one patient died within 30 d after *** overall median survival was 4 mo,whereas the median survival of R0 resected patients was 16 *** overall 1-,2-and 3-year cumulative survival rates were 67%,17% and 17%,*** rates were significantly associated with curative resection (P=0.002),intrahepatic tumor (P=0.003),negative margin status (P=0.013),early tumor stage (P=0.016),higher tumor differentiation (P=0.032) and absence of jaundice (P=0.038).Multivariate analysis showed that tumor location was a significant independent predictor of patient ***:Curative,margin-negative resection of early stage,well-differentiated intrahepatic tumors is associated with improved patient survival.

关键词：马来西亚胆管生存分析平均存活时间癌多元统计分析临床特点影响因素

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