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NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription

Fili, Natalia, Gupta, Yukti-Hari, dos Santos, Alia, Cook, Alexander, Poland, Simon, Ameer-Beg, Simon, Parsons, Maddy, Toseland, Christopher P. (2017) NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription. Nature Communications, 8 . Article Number 1871. ISSN 2041-1723. (doi:10.1038/s41467-017-02050-w) (KAR id:64916)

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Official URL
http://dx.doi.org/10.1038/s41467-017-02050-w

Abstract

Myosin VI (MVI) has been found to be overexpressed in ovarian, breast and prostate cancers. Moreover, it has been shown to play a role in regulating cell proliferation and migration, and to interact with RNA Polymerase II (RNAPII). Here, we find that backfolding of MVI regulates its ability to bind DNA and that a putative transcription co-activator NDP52 relieves the auto-inhibition of MVI to enable DNA binding. Additionally, we show that the MVI–NDP52 complex binds RNAPII, which is critical for transcription, and that depletion of NDP52 or MVI reduces steady-state mRNA levels. Lastly, we demonstrate that MVI directly interacts with nuclear receptors to drive expression of target genes, thereby suggesting a link to cell proliferation and migration. Overall, we suggest MVI may function as an auxiliary motor to drive transcription.

Item Type: Article
DOI/Identification number: 10.1038/s41467-017-02050-w
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Chris Toseland
Date Deposited: 30 Nov 2017 14:54 UTC
Last Modified: 05 Oct 2020 14:39 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/64916 (The current URI for this page, for reference purposes)
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