|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | LncRNAs-directed PTEN enzymatic switch governs epithelial–mesenchymal transition显示文摘Despite the structural conservation of PTEN with dual-specificity phosphatases,there have been no reports regarding the regulatory mechanisms that underlie this potential dual-phosphatase activity.Here,we report that K27-linked polyubiquitination of PTEN at lysines 66 and 80 switches its phosphoinositide/protein tyrosine phosphatase activity to protein serine/threonine phosphatase activity.Mechanistically,high glucose,TGF-β,CTGF,SHH,and IL-6 induce the expression of a long non-coding RNA,GAEA(Glucose Aroused for EMT Activation),which associates with an RNA-binding E3 ligase,MEX3C,and enhances its enzymatic activity,leading to the K27-linked polyubiquitination of PTEN.The MEX3C-catalyzed PTEN^K27-polyUb activates its protein serine/threonine phosphatase activity and inhibits its phosphatidylinositol/protein tyrosine phosphatase activity.With this altered enzymatic activity,PTEN^K27-polyUb dephosphorylates the phosphoserine/threonine residues of TWIST1,SNAI1,and YAP1,leading to accumulation of these master regulators of EMT.Animals with genetic inhibition of PTEN^K27-polyUb,by a single nucleotide mutation generated using CRISPR/Cas9(Pten^K80R/K80R),exhibit inhibition of EMT markers during mammary gland morphogenesis in pregnancy/lactation and during cutaneous wound healing processes.Our findings illustrate an unexpected paradigm in which the lncRNA-dependent switch in PTEN protein serine/threonine phosphatase activity is important for physiological homeostasis and disease development. | Qingsong Hu Chunlai Li Shouyu Wang Yajuan Li Bo Wen Yanyan Zhang Ke Liang Jun Yao Youqiong Ye Heidi Hsiao Tina K.Nguyen Peter K.Park Sergey D.Egranov David H.Hawke Jeffrey R.Marks Leng Han Mien-Chie Hung Bing Zhang Chunru Lin Liuqing Yang | 2019 | Cell Research2019，29，4： | 8 |
| 2 | Development of peptide inhibitors of HIV transmission显示文摘Treatment of HIV has long faced the challenge of high mutation rates leading to rapid development of resistance,with ongoing need to develop new methods to effectively fight the infection.Traditionally,early HIV medications were designed to inhibit RNA replication and protein production through small molecular drugs.Peptide based therapeutics are a versatile,promising field in HIV therapy,which continues to develop as we expand our understanding of key protein-protein interactions that occur in HIV replication and infection.This review begins with an introduction to HIV,followed by the biological basis of disease,current clinical management of the disease,therapeutics on the market,and finally potential avenues for improved drug development. | Siyu Shi Peter K.Nguyen Henry J.Cabral Ramon Diez-Barroso Paul J.Derry Satoko M.Kanahara Vivek A.Kumar | 2016 | Bioactive Materials2016，1，2： | 2 |
| 3 | Network rewiring,adaptive resistance and combating strategies in breast cancer显示文摘Resistance to targeted anti-cancer drugs is a complex phenomenon and a major challenge in cancer treatment.It is becoming increasingly evident that a form of acquired drug resistance known as“adaptive resistance”is a common cause of treatment failure and patient relapse in many cancers.Unlike classical resistance mechanisms that are acquired via genomic alterations,adaptive resistance is instead driven by non-genomic changes involving rapid and dynamic rewiring of signalling and/or transcriptional networks following therapy,enabled by complex pathway crosstalk and feedback regulation.Such network rewiring allows tumour cells to adapt to the drug treatment,circumvent the initial drug challenge and continue to survive in the presence of the drug.Despite its great clinical importance,adaptive resistance remains largely under-studied and poorly defined.This review is focused on recent findings which provide new insights into the mechanisms underlying adaptive resistance in breast cancer,highlighting how breast tumour cells rewire intracellular signalling pathways to overcome the stress of initial targeted therapy.In particular,we investigate adaptive resistance to targeted inhibition of two major oncogenic signalling axes frequently dysregulated in breast cancer,the PI3K-AKT-mTOR and RAS-MAPK signalling pathways;and discuss potential combination treatment strategies that overcome such resistance.In addition,we highlight application of quantitative and computational modelling as a novel integrative and powerful approach to gain network-level understanding of network rewiring,and rationally identify and prioritise effective drug combinations. | Constance Gaya Cremers Lan K.Nguyen | 2019 | Cancer Drug Resistance2019，2，4： | 1 |
| 4 | Response to pegylated interferon and ribavirin in Asian American patients with Chronic hepatitis C genotypes 1 vs 2/3 vs 6显示文摘 | N. H.Nguyen P.VuTien R. T.Garcia H.Trinh H.Nguyen K.Nguyen B.Levitt M. H.Nguyen | 2010 | Journal of Viral Hepatitis2010，，10： | 1 |
| 5 | Low‐dose computed tomography versus plain abdominal radiography in the investigation of an acute abdomen显示文摘 | Long K.Nguyen Daniel D.Wong Daniel M.Fatovich Justin M.Yeung JenniferPersaud Christopher J.Wood Davidde Vos Richard M.Mendelson | 2012 | ANZ Journal of Surgery (鈥?)2012，，1： | 1 |
| 6 | Defining the Conditions for the Generation of Melanocytes from Human Embryonic Stem Cells显示文摘 | DongFang KimLeishear Thiennga K.Nguyen RenaFinko KunCai MizuhoFukunaga LingLi Patricia A.Brafford Angela N.Kulp XiaoweiXu Keiran S. M.Smalley MeenhardHerlyn | 2009 | STEM CELLS2009，，7： | 1 |
| 7 | β‐Catenin Signaling Increases in Proliferating NG2+ Progenitors and Astrocytes during Post‐Traumatic Gliogenesis in the Adult Brain显示文摘 | Bryan D.White Ryan J.Nathe Don O.Maris Nghi K.Nguyen Jamie M.Goodson Randall T.Moon Philip J.Horner | 2010 | STEM CELLS2010，，2： | 1 |
| 8 | Low‐dose computed tomography versus plain abdominal radiography in the investigation of an acute abdomen显示文摘 | Long K.Nguyen Daniel D.Wong Daniel M.Fatovich Justin M.Yeung JenniferPersaud Christopher J.Wood Davidde Vos Richard M.Mendelson | 2012 | 2012 (1‐2)2012，，1： | 1 |
| 9 | Low‐dose computed tomography versus plain abdominal radiography in the investigation of an acute abdomen显示文摘 | Long K.Nguyen Daniel D.Wong Daniel M.Fatovich Justin M.Yeung JenniferPersaud Christopher J.Wood Davidde Vos Richard M.Mendelson | 2012 | ANZ Journal of Surgery (鈥?)2012，，1： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员