NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription.
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.
Mesh Terms:
Animals, Cell Nucleus, DNA, Gene Knockdown Techniques, HeLa Cells, Humans, MCF-7 Cells, Myosin Heavy Chains, Nuclear Proteins, Protein Folding, RNA Polymerase II, Sf9 Cells, Spodoptera, Transcription, Genetic, Transcriptional Activation
Animals, Cell Nucleus, DNA, Gene Knockdown Techniques, HeLa Cells, Humans, MCF-7 Cells, Myosin Heavy Chains, Nuclear Proteins, Protein Folding, RNA Polymerase II, Sf9 Cells, Spodoptera, Transcription, Genetic, Transcriptional Activation
Nat Commun
Date: Dec. 30, 2016
PubMed ID: 29187741
View in: Pubmed Google Scholar
Download Curated Data For This Publication
214647
Switch View:
- Interactions 9