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Dong et al. Vessel Plus 2017;1:3-11 Vessel Plus
DOI: 10.20517/2574-1209.2016.01
www.vpjournal.net
Review Open Access

Mimetic peptide of ubiquitin-interacting

motif of epsin as a cancer therapeutic-

perspective in brain tumor therapy through

regulating VEGFR2 signaling

Yunzhou Dong , Hao Wu , Jerry Dong , Kai Song , Habibunnabi Ashiqur Rahman , Rheal Towner , Hong Chen 1
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1 Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
2 Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA.
Correspondence to: Dr. Yunzhou Dong or Dr. Hong Chen, Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Harvard
Medical School, Boston, MA 02115, USA. E-mail: yunzhou.dong@childrens.harvard.edu; hong.chen@childrens.harvard.edu
How to cite this article: Dong Y, Wu H, Dong J, Song K, Rahman HA, Towner R, Chen H. Mimetic peptide of ubiquitin-interacting motif of epsin as
a cancer therapeutic-perspective in brain tumor therapy through regulating VEGFR2 signaling. Vessel Plus 2017;1:3-11.
Dr. Yunzhou Dong is a senior investigator at the Vascular Biology Program of Boston Children’s Hospital and
Harvard Medical School. He received his PhD in Genetics and Molecular Biology in 2000. Dr. Dong had worked
at the Cardiovascular Biology Program in the Oklahoma Medical Research Foundation (OMRF) and the Section
of Endocrinology and Diabetes in the University of Oklahoma Health Sciences Center. In his earlier career, Dr.
Dong worked at the College of Veterinary Medicine, University of Tennessee at Knoxville. Dr. Dong has substantial
publications in prestigious journals about the mechanistic study and therapeutic development in cardiovascular
diseases, metabolic diseases and cancer field.

ABSTRACT
Article history: Epsins, endocytic adaptor proteins required for internalization of ubiquitylated receptors, are
Received: 31-08-2016 generally upregulated in human cancers. It has been characterized that mice deficient of epsins
Accepted: 01-11-2016 in the endothelium inhibit tumor growth by dysregulating vascular endothelial growth factor
Published: 31-03-2017 receptor-2 (VEGFR2) signaling and non-productive tumor angiogenesis. Binding of the epsin
ubiquitin (Ub)-interacting motif (UIM) with ubiquitylated VEGFR2 is a critical mechanism
Key words: for epsin-dependent VEGFR2 endocytosis and degradation, indicative of epsin UIM as a
UPI peptide, potential therapeutic target. A Computer Assisted Drug Design approach was utilized to create
epsin, the UIM mimetic peptides for the functional competition of epsin binding sites in ubiquitylated
cancer therapy, VEGFR2 in vivo. Specifically targeting VEGFR2 in the tumor vasculature, the chemically
glioma, synthesized chimeric UIM peptide, UPI, causes non-functional tumor angiogenesis, retards
tumor growth, and increases survival rates in several tumor models. The authors showed
tumor angiogenesis
that UPI binds ubiquitylated VEGFR2 to form a supercomplex in an Ub-dependent fashion.
Collectively, the UPI targeting strategy offers a potentially novel treatment for cancer patients
who are resistant to current anti-angiogenic therapies. In this review, the authors outline the
main points of this research specifically as a potential application for glioma tumor therapy.

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