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Tytuł:
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Dual specificity phosphatase 9: A novel binding partner cum substrate of proapoptotic serine protease HtrA2.
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Autorzy:
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Acharya S; Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, 400094, India.
Dutta S; Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India.
Mudrale SP; Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India.
Bose K; Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, 400094, India. Electronic address: .
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Źródło:
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Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Dec 10; Vol. 533 (3), pp. 607-612. Date of Electronic Publication: 2020 Sep 26.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
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MeSH Terms:
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Dual-Specificity Phosphatases/*metabolism
High-Temperature Requirement A Serine Peptidase 2/*metabolism
Mitogen-Activated Protein Kinase Phosphatases/*metabolism
Binding Sites ; Computer Simulation ; Dual-Specificity Phosphatases/chemistry ; High-Temperature Requirement A Serine Peptidase 2/chemistry ; Humans ; Mitogen-Activated Protein Kinase Phosphatases/chemistry ; Models, Molecular ; Proteome
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Contributed Indexing:
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Keywords: Binding specificity; DUSP9; HtrA2; Novel binding partner; Substrate
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Substance Nomenclature:
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0 (Proteome)
EC 3.1.3.16 (Mitogen-Activated Protein Kinase Phosphatases)
EC 3.1.3.48 (DUSP9 protein, human)
EC 3.1.3.48 (Dual-Specificity Phosphatases)
EC 3.4.21.108 (HTRA2 protein, human)
EC 3.4.21.108 (High-Temperature Requirement A Serine Peptidase 2)
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Entry Date(s):
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Date Created: 20200929 Date Completed: 20210315 Latest Revision: 20210315
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Update Code:
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20240105
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DOI:
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10.1016/j.bbrc.2020.09.062
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PMID:
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32988583
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Human high temperature requirement protease A2 (HtrA2) is a trimeric PDZ bearing proapoptotic serine protease, which is involved in various cellular processes and pathologies. Research in the last decade strongly advocates its role as a potential therapeutic target and therefore warrants the need to minutely investigate its mechanism of action, regulation, interactions with other proteins and its binding specificities. In this particular study, we adopted an in silico approach to predict novel interacting partners and/or substrates of HtrA2 by building a peptide library using a binding pattern search. This library was used to look for novel ligand proteins in the human proteome. Thereafter, the putative interaction was validated using biochemical and cell-based studies. In a first, here we report that HtrA2 shows robust interactions with DUSP9 (Dual specificity phosphatase 9) in GST-pulldown and Co-Immunoprecipitation (Co-IP) experiments and cleaves it in vitro. Besides, we also provided a detailed characterization of the interaction interface. Moreover, this study in general provides an efficient, fast and practical method of candidate ligand library screening for exploring the binding properties of HtrA2.
Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
