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Regulation of poly ADP-ribosylation of VEGF by an interplay between PARP-16 and TNKS-2

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Abstract

The biological activity of vascular endothelial growth factor (VEGF), the major cytokine regulating the process of angiogenesis is tightly controlled at multiple levels including processes involving post-translational modification such as ADP-ribosylation and glycosylation. ADP-ribosylation is a reversible NAD+-dependent modification, catalyzed by poly ADP-ribose polymerase (PARP) or ADP-ribosyl transferase (ADPRTs) and has been reported by us and others as a modification that reduces the biological activity of VEGF. The factors responsible for any such modification should occur in the secretory pathway, i.e., in the endoplasmic reticulum and Golgi. Our investigation carried out in this direction revealed that ADP-ribosylation of VEGF requires the interplay between members of poly ADP-ribose polymerase (PARP) family in the secretory pathway, viz., ER associated PARP-16 and Golgi associated Tankyrase-2 (TNKS-2). The data presented in this manuscript suggest that PARP-16 catalysis the priming mono ADP-ribosylation of VEGF which is a prerequisite for poly ADP-ribosylation of VEGF by TNKS-2.

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Acknowledgement

Financial assistance received from DST-SERB (SB/YS/LS-367/2013) is gratefully acknowledged. Financial assistance from DST, Govt. of India in the form of fellowship to Vishnu is also thankfully acknowledged.

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Author notes

  1. Haritha Kunhiraman

    Present address: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, John Hopkins University, 1650 Orleans St., Baltimore, MD, 21231, USA

  2. Haritha Kunhiraman

    Present address: Cancer and Blood Disorder Institute, Johns Hopkins All Children’s Hospital, 600 5th St. South, St. Petersburg, FL, 33701, USA

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Central University of Kerala, Tejaswini Hills, Periya, Kasargod, Kerala, India

    Haritha Kunhiraman, Vishnu Ramachandran, Lincy Edatt & V. B. Sameer Kumar

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  1. Haritha Kunhiraman
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  2. Vishnu Ramachandran
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Correspondence to V. B. Sameer Kumar.

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Kunhiraman, H., Ramachandran, V., Edatt, L. et al. Regulation of poly ADP-ribosylation of VEGF by an interplay between PARP-16 and TNKS-2. Mol Cell Biochem 471, 15–27 (2020). https://doi.org/10.1007/s11010-020-03746-2

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  • DOI: https://doi.org/10.1007/s11010-020-03746-2

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