Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I

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title = "Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I",
abstract = "Ribosome biogenesis is essential for cell growth and proliferation and is commonly elevated in cancer. Accordingly, numerous oncogene and tumor suppressor signaling pathways target rRNA synthesis. In breast cancer, non-canonical Wnt signaling by Wnt5a has been reported to antagonize tumor growth. Here, we show that Wnt5a rapidly represses rDNA gene transcription in breast cancer cells and generates a chromatin state with reduced transcription of rDNA by RNA polymerase I (Pol I). These effects were specifically dependent on Dishevelled1 (DVL1), which accumulates in nucleolar organizer regions (NORs) and binds to rDNA regions of the chromosome. Upon DVL1 binding, the Pol I transcription activator and deacetylase Sirtuin 7 (SIRT7) releases from rDNA loci, concomitant with disassembly of Pol I transcription machinery at the rDNA promoter. These findings reveal that Wnt5a signals through DVL1 to suppress rRNA transcription. This provides a novel mechanism for how Wnt5a exerts tumor suppressive effects and why disruption of Wnt5a signaling enhances mammary tumor growth in vivo.",
author = "Dass, {Randall A.} and Sarshad, {Aishe A.} and Carson, {Brittany B.} and Feenstra, {Jennifer M.} and Amanpreet Kaur and Ales Obrdlik and Parks, {Matthew M.} and Varsha Prakash and Love, {Damon K.} and Kristian Pietras and Rosa Serra and Blanchard, {Scott C.} and Piergiorgio Percipalle and Brown, {Anthony M C} and Vincent, {C. Theresa}",
year = "2016",
month = "8",
day = "1",
doi = "10.1371/journal.pgen.1006217",
language = "English",
volume = "12",
journal = "PLoS Genetics",
issn = "1553-7404",
publisher = "Public Library of Science",
number = "8",