The intracellular domain of β-dystroglycan mediates the nucleolar stress response by suppressing UBF transcriptional activity

Cell Death & Disease
Paulina Margarita Azuara-MedinaBulmaro Cisneros

Abstract

β-dystroglycan (β-DG) is a key component of multiprotein complexes in the plasma membrane and nuclear envelope. In addition, β-DG undergoes two successive proteolytic cleavages that result in the liberation of its intracellular domain (ICD) into the cytosol and nucleus. However, stimuli-inducing ICD cleavage and the physiological relevance of this proteolytic fragment are largely unknown. In this study we show for the first time that β-DG ICD is targeted to the nucleolus where it interacts with the nuclear proteins B23 and UBF (central factor of Pol I-mediated rRNA gene transcription) and binds to rDNA promoter regions. Interestingly DG silencing results in reduced B23 and UBF levels and aberrant nucleolar morphology. Furthermore, β-DG ICD cleavage is induced by different nucleolar stressors, including oxidative stress, acidosis, and UV irradiation, which implies its participation in the response to nucleolar stress. Consistent with this idea, overexpression of β-DG elicited mislocalization and decreased levels of UBF and suppression of rRNA expression, which in turn provoked altered ribosome profiling and decreased cell growth. Collectively our data reveal that β-DG ICD acts as negative regulator of rDNA transcription by imped...Continue Reading

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Citations

Jul 28, 2019·Neuromolecular Medicine·Yan Jun Lee, Toh Hean Ch'ng
Mar 16, 2021·Animal Cells and Systems·Eunyoung Lee, Do Hee Lee

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Methods Mentioned

BETA
confocal microscopy
immunoprecipitation
transfection
ChIP
PCR
Assay
transfections

Software Mentioned

ImageJ
Prism6
StepOne
Multiplot

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