The uncharacterized protein ZNF200 interacts with PRMT3 and aids its stability and nuclear translocation.

Autor:	Gupta S; Department of Biotechnology, Pondicherry University, Puducherry 605 014, India., Verma M; Department of Biotechnology, Pondicherry University, Puducherry 605 014, India., Kadumuri RV; Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517 507, Andhra Pradesh, India., Chutani N; Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517 507, Andhra Pradesh, India., Khan MIK; Department of Biotechnology, Pondicherry University, Puducherry 605 014, India., Chavali S; Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517 507, Andhra Pradesh, India., Dhayalan A; Department of Biotechnology, Pondicherry University, Puducherry 605 014, India.
Jazyk:	angličtina
Zdroj:	The Biochemical journal [Biochem J] 2024 Dec 04; Vol. 481 (23), pp. 1723-1740.
DOI:	10.1042/BCJ20240476
Abstrakt:	Protein arginine methyltransferase 3 (PRMT3), a type I arginine methyltransferase is localized predominantly in the cytoplasm and regulates different cellular functions. Nevertheless, PRMT3 also exhibits regulatory functions in the nucleus by interacting with the liver X receptor alpha (LXRα) and catalyzes asymmetric dimethylation modifications at arginine 3 of histone 4 (H4R3me2a). However, very little is known about the regulation of the versatile global regulator PRMT3 and how PRMT3 is translocated to the nucleus. In this study, we identified ZNF200, a hitherto uncharacterized protein, as a potential binding partner of PRMT3 through yeast two-hybrid screening. We confirmed the interaction of PRMT3 with ZNF200 using immunoprecipitation and in vitro pull-down experiments. GST pull-down experiments and molecular docking studies revealed that the N-terminal zinc finger domain of PRMT3 binds to the C-terminal zinc finger regions of ZNF200. Furthermore, the evolutionary conservation of the Znf domain of PRMT3 correlates with the emergence of ZNF200 in mammals. We found that ZNF200 stabilizes PRMT3 by inhibiting its proteasomal degradation. ZNF200, a nuclear-predominant protein, promotes the nuclear translocation of PRMT3, leading to the global increase of H4R3me2a modifications. These findings imply that ZNF200 is a critical regulator of the steady-state levels and nuclear and epigenetic functions of PRMT3. (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
Databáze:	MEDLINE
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