Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 intracellular ATP levels. Collectively, our study demonstrates that endostatin has novel ATPase activity, which mediates its antiangiogenic and antitumor activities, suggesting that construction of endostatin analogues with high ATPase activity may provide a new direction for the development of more potent antiangiogenic drugs.
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PMID:Endostatin has ATPase activity, which mediates its antiangiogenic and antitumor activities. 2578 76

Background- Endostatin by virtue of their therapeutic value against rheumatoid arthritis have recently generated enormous interest among biomedical science. Recent study revealed that various approaches have been made to prevent rheumatoid arthritis by either controlling or inhibiting the progression of angiogenesis. Objective- The main objective of the current manuscript is to enumerates the intrinsic role of endostatin in rheumatoid arthritis. Method- A thorough and detailed review of literature from the papers published from the year 1997-2019 was studied for preparation of the current article. Result- Endostatin is one such agent of subfamily of ECM called as multiplexins obtained from proteolytic cleavage of XVIII and its carboxylic terminal fragments and is known for its antiangiogenic and antiproliferative property. The exact mechanism of endostatin is still unclear but it acts by downregulating or inhibiting the responses of various factors including Id1, Id3, matrix metalloproteinase and Nuclear factor Kappa B that are liable for angiogenesis. The mutual effects on adipogenesis and angiogenesis, endostatin inhibits dietary induced obesity and its related metabolic disorders, such as insulin resistance, glucose intolerance and hepatic steatosis. Conclusion-The present review demonstrates the intrinsic usage of endostatin as a novel molecule in rheumatoid arthritis and focus on the status of the therapeutic potential of endostatin in inhibiting the activity of angiogenesis is also very well explored.
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PMID:Role Of Endostatin In Rheumatoid Arthritis. 3234 30