Endostatin has ATPase activity, which mediates its antiangiogenic and antitumor activities

Molecular Cancer Therapeutics
Shan WangYongzhang Luo

Abstract

Endostatin is an endogenous angiogenesis inhibitor with broad-spectrum antitumor activities. Although the molecular mechanisms of endostatin have been extensively explored, the intrinsic biochemical characteristics of endostatin are not completely understood. Here, we revealed for the first time that endostatin embedded novel ATPase activity. Moreover, mutagenesis study showed that the ATPase activity of endostatin mutants positively correlated with effects on endothelial cell activities and tumor growth. E-M, an endostatin mutant with higher ATPase activity than that of wild-type (WT) endostatin, significantly increased endostatin-mediated inhibitory effects on endothelial cell proliferation, migration, tube formation, and adhesion. In vivo study showed that E-M displayed enhanced antitumor effects compared with WT. On the other hand, K96A, K96R, and E176A, endostatin mutants with lower ATPase activities than that of WT, showed reduced or comparable effects on targeting both in vitro endothelial cell activities and in vivo tumor angiogenesis and tumor growth. Furthermore, endostatin and its mutants exhibited distinct abilities in regulations of gene expression (Id1, Id3), cell signaling (Erk, p38, and Src phosphorylation), and...Continue Reading

References

Jan 31, 1995·Proceedings of the National Academy of Sciences of the United States of America·D E ChampagneA A James
Nov 15, 1994·Biochemical and Biophysical Research Communications·K KomatsuC A Strott
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·Y H DingD C Wiley
May 4, 2001·The Journal of Biological Chemistry·N J MacDonaldB K Sim
May 5, 2001·Molecular Cell·S A KarumanchiV P Sukhatme
Feb 13, 2002·Oncogene·R BenezraD Lyden
May 25, 2002·The Journal of Biological Chemistry·Young-Mi KimYoung-Guen Kwon
Sep 19, 2002·The Journal of Biological Chemistry·Kashi JavaherianKin-Ming Lo
Apr 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Akulapalli SudhakarRaghu Kalluri
Oct 22, 2003·Journal of Molecular Biology·Detlef D LeipeL Aravind
Jan 30, 2004·The Journal of Nutrition·Susan M GaleChristos S Mantzoros
Mar 17, 2004·Molecular Cell·Amir AbdollahiPeter E Huber
Aug 3, 2005·Nature Reviews. Molecular Cell Biology·Phyllis I Hanson, Sidney W Whiteheart
Dec 27, 2005·Experimental Cell Research·Judah Folkman
Feb 9, 2006·Nature Biotechnology·Hepeng Jia, Jim Kling
Apr 3, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shaopeng YuanYongzhang Luo
Mar 18, 2009·Methods in Enzymology·Enrique M De La Cruz, E Michael Ostap
May 28, 2009·IUBMB Life·Yan FuYongzhang Luo
Apr 8, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Weiyi Liu, Paul Collodi
May 3, 2011·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Baohui HanXianqiao Jin
May 15, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Chuanliang CuiJun Guo

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Citations

Sep 19, 2015·Biochimie·Sylvie Ricard-Blum, Sylvain D Vallet
Feb 13, 2016·Frontiers in Pharmacology·Sylvie Ricard-Blum, Sylvain D Vallet
Sep 15, 2015·Biochimica Et Biophysica Acta·Amit WaliaDimitri T Azar
Sep 15, 2016·Expert Review of Hematology·E Carlos Rodriguez-Merchan
Aug 4, 2018·Clinical and Experimental Pharmacology & Physiology·Hao HuangBai-Jun Fang
Jan 11, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Joo Hyoung LeeSelvarangan Ponnazhagan
Jun 23, 2019·Cells·Jeannette HuamanOlorunseun O Ogunwobi
Feb 17, 2021·Nature Reviews. Cancer·Thomas R Cox
Nov 15, 2017·Matrix Biology : Journal of the International Society for Matrix Biology·Sylvie Ricard-Blum, Sylvain D Vallet

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