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SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis

Author

Listed:
  • Huanjiao Jenny Zhou

    (Yale University School of Medicine)

  • Zhe Xu

    (Yale University School of Medicine
    First Affiliated Hospital of Jinan University)

  • Zongren Wang

    (Yale University School of Medicine
    Sun Yat-sen University)

  • Haifeng Zhang

    (Yale University School of Medicine)

  • Zhen W. Zhuang

    (Yale University School of Medicine)

  • Michael Simons

    (Yale University School of Medicine)

  • Wang Min

    (Yale University School of Medicine
    Sun Yat-sen University)

Abstract

Regulation of VEGFR2 represents an important mechanism for the control of angiogenesis. VEGFR2 activity can be regulated by post-translational modifications such as ubiquitination and acetylation. However, whether VEGFR2 can be regulated by SUMOylation has not been investigated. Here we show that endothelial-specific deletion of the SUMO endopeptidase SENP1 reduces pathological angiogenesis and tissue repair during hindlimb ischemia, and VEGF-induced angiogenesis in the cornea, retina, and ear. SENP1-deficient endothelial cells show increased SUMOylation of VEGFR2 and impaired VEGFR2 signalling. SUMOylation at lysine 1270 retains VEGFR2 in the Golgi and reduces its surface expression, attenuating VEGFR2-dependent signalling. Moreover, we find that SENP1 is downregulated and VEGFR2 hyper-SUMOylated in diabetic settings and that expression of a non-SUMOylated form of VEGFR2 rescues angiogenic defects in diabetic mice. These results show that VEGFR2 is regulated by deSUMOylation during pathological angiogenesis, and propose SENP1 as a potential therapeutic target for the treatment of diabetes-associated angiogenesis.

Suggested Citation

  • Huanjiao Jenny Zhou & Zhe Xu & Zongren Wang & Haifeng Zhang & Zhen W. Zhuang & Michael Simons & Wang Min, 2018. "SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05812-2
    DOI: 10.1038/s41467-018-05812-2
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    Cited by:

    1. Suchitra Mohanty & Sujit Suklabaidya & Alfonso Lavorgna & Takaharu Ueno & Jun-ichi Fujisawa & Nyater Ngouth & Steven Jacobson & Edward W. Harhaj, 2024. "The tyrosine kinase KDR is essential for the survival of HTLV-1-infected T cells by stabilizing the Tax oncoprotein," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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