Ubiquitin C‐Terminal Hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine‐Based Inhibitor
作者： Aaron D. Krabill , Hao Chen , Sajjad Hussain , Chao Feng , Ammara Abdullah
关键词: Ubiquitin C-Terminal Hydrolase 、 Oncogene 、 Hydrolase 、 Structural biology 、 Cancer 、 Chemistry 、 Cancer research 、 In vivo 、 Ubiquitin 、 Deubiquitinating enzyme
摘要: The deubiquitinase (DUB) ubiquitin C-terminal hydrolase L1 (UCHL1) is expressed primarily in the central nervous system under normal physiological conditions. However, UCHL1 overexpressed various aggressive forms of cancer with strong evidence supporting as an oncogene lung, glioma, and blood cancers. In particular, level expression these cancers correlates increased invasiveness metastatic behavior, well poor patient prognosis. Although considered potential a therapeutic target, there remains significant lack useful small-molecule probes to pharmacologically validate vivo targeting enzyme. Herein, we describe characterization new covalent cyanopyrrolidine-based inhibitory scaffold biochemical cellular studies better understand utility this inhibitor elucidating role biology.
sci-hub.se 参考文章(65)
Junji Iwahara, Jonathan M. Wojciak, Robert T. Clubb, Improved NMR spectra of a protein-DNA complex through rational mutagenesis and the application of a sensitivity optimized isotope-filtered NOESY experiment. Journal of Biomolecular NMR. ,vol. 19, pp. 231- 241 ,(2001) , 10.1023/A:1011296112710
Cheryl H Arrowsmith, James E Audia, Christopher Austin, Jonathan Baell, Jonathan Bennett, Julian Blagg, Chas Bountra, Paul E Brennan, Peter J Brown, Mark E Bunnage, Carolyn Buser-Doepner, Robert M Campbell, Adrian J Carter, Philip Cohen, Robert A Copeland, Ben Cravatt, Jayme L Dahlin, Dashyant Dhanak, Aled M Edwards, Mathias Frederiksen, Stephen V Frye, Nathanael Gray, Charles E Grimshaw, David Hepworth, Trevor Howe, Kilian V M Huber, Jian Jin, Stefan Knapp, Joanne D Kotz, Ryan G Kruger, Derek Lowe, Mary M Mader, Brian Marsden, Anke Mueller-Fahrnow, Susanne Müller, Ronan C O'Hagan, John P Overington, Dafydd R Owen, Saul H Rosenberg, Ruth Ross, Bryan Roth, Matthieu Schapira, Stuart L Schreiber, Brian Shoichet, Michael Sundström, Giulio Superti-Furga, Jack Taunton, Leticia Toledo-Sherman, Chris Walpole, Michael A Walters, Timothy M Willson, Paul Workman, Robert N Young, William J Zuercher, The promise and peril of chemical probes. Nature Chemical Biology. ,vol. 11, pp. 536- 541 ,(2015) , 10.1038/NCHEMBIO.1867
Sajjad Hussain, Tibor Bedekovics, Marta Chesi, P. Leif Bergsagel, Paul J. Galardy, UCHL1 is a biomarker of aggressive multiple myeloma required for disease progression Oncotarget. ,vol. 6, pp. 40704- 40718 ,(2015) , 10.18632/ONCOTARGET.5727
Hyun Jung Kim, Venkataraman Magesh, Jae-Jin Lee, Sun Kim, Ulla G. Knaus, Kong-Joo Lee, Ubiquitin C-terminal hydrolase-L1 increases cancer cell invasion by modulating hydrogen peroxide generated via NADPH oxidase 4. Oncotarget. ,vol. 6, pp. 16287- 16303 ,(2015) , 10.18632/ONCOTARGET.3843
Fredrik I. Andersson, Elizabeth F. Werrell, Lindsay McMorran, William J.K. Crone, Chittarnajan Das, Shang-Te Danny Hsu, Sophie E. Jackson, The effect of Parkinson's-disease-associated mutations on the deubiquitinating enzyme UCH-L1. Journal of Molecular Biology. ,vol. 407, pp. 261- 272 ,(2011) , 10.1016/J.JMB.2010.12.029
K. Wilkinson, K. Lee, S Deshpande, P Duerksen-Hughes, J. Boss, J Pohl, The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase Science. ,vol. 246, pp. 670- 673 ,(1989) , 10.1126/SCIENCE.2530630
Ara H. Mermerian, April Case, Ross L. Stein, Gregory D. Cuny, Structure–activity relationship, kinetic mechanism, and selectivity for a new class of ubiquitin C-terminal hydrolase-L1 (UCH-L1) inhibitors Bioorganic & Medicinal Chemistry Letters. ,vol. 17, pp. 3729- 3732 ,(2007) , 10.1016/J.BMCL.2007.04.027
H J Kim, Y M Kim, S Lim, Y K Nam, J Jeong, H-J Kim, K-J Lee, Ubiquitin C-terminal hydrolase-L1 is a key regulator of tumor cell invasion and metastasis. Oncogene. ,vol. 28, pp. 117- 127 ,(2009) , 10.1038/ONC.2008.364
Huang-Chun Lien, Chung-Chieh Wang, Ching-Hung Lin, Yen-Shen Lu, Chiun-Sheng Huang, Li-Ping Hsiao, Yu-Tung Yao, Differential expression of ubiquitin carboxy-terminal hydrolase L1 in breast carcinoma and its biological significance ☆ ☆☆ Human Pathology. ,vol. 44, pp. 1838- 1848 ,(2013) , 10.1016/J.HUMPATH.2013.02.006
Catherine Zwahlen, Pascale Legault, Sébastien J. F. Vincent, Jack Greenblatt, Robert Konrat, Lewis E. Kay, Methods for Measurement of Intermolecular NOEs by Multinuclear NMR Spectroscopy: Application to a Bacteriophage λ N-Peptide/boxB RNA Complex Journal of the American Chemical Society. ,vol. 119, pp. 6711- 6721 ,(1997) , 10.1021/JA970224Q