The Wnt/β-Catenin Pathway is Activated as a Novel Nucleolar Stress Response.
Abstract
Ribosomes are mandatory for growth and survival. The complex process of ribosome biogenesis is located in nucleoli and requires action of the RNA polymerases I-III, together with a multitude of processing factors involved in rRNA cleavage and maturation. Impaired ribosome biogenesis and loss of nucleolar integrity triggers nucleolar stress, which classically stabilizes the tumor suppressor p53 and induces cell cycle arrest and apoptosis. Nucleolar stress is implemented in modern anti-cancer therapies, however, also emerges as contributor to diverse pathological conditions. These include ribosomopathies, such as the Shwachman Bodian Diamond Syndrome (SBDS), which are not only characterized by nucleolar stress, but paradoxically also increased cancer incidence. Wnt signaling is tightly coupled to cell proliferation and is constitutively activated in various tumor types. In addition, the Wnt/β-Catenin pathway regulates ribosome formation. Here, we demonstrate that induction of nucleolar stress by different strategies stimulates the Wnt/β-Catenin pathway. We show that depletion of the key ribosomopathy factor SBDS, or the nucleolar factors Nucleophosmin (NPM), Pescadillo 1 (PES1) or Peter Pan (PPAN) by si RNA-mediated knockdown or ...Continue Reading
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Dynamic sorting of nuclear components into distinct nucleolar caps during transcriptional inhibition
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