Margarita Azuara-Medina, Paulina and Maria Sandoval-Duarte, Ariana and Morales-Lazaro, Sara L. and Modragon-Gonzalez, Ricardo and Velez-Aguilera, Griselda and de Dios Gomez-Lopez, Juan and Elizabeth Jimenez-Gutierrez, Guadalupe and Tiburcio-Felix, Reynaldo and Martinez-Vieyra, Ivette and Suarez-Sanchez, Rocio and Laengst, Gernot and Javier Magana, Jonathan and Winder, Steve J. and Ortega, Arturo and Ramos Perlingeiro, Rita de Cassia and Jacobs, Laura A. and Cisneros, Bulmaro (2019) The intracellular domain of beta-dystroglycan mediates the nucleolar stress response by suppressing UBF transcriptional activity. CELL DEATH & DISEASE, 10: 196. ISSN 2041-4889,
Full text not available from this repository. (Request a copy)Abstract
beta-dystroglycan (beta-DG) is a key component of multiprotein complexes in the plasma membrane and nuclear envelope. In addition, beta-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 beta-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, beta-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 beta-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 beta-DG ICD acts as negative regulator of rDNA transcription by impeding the transcriptional activity of UBF, as a part of the protective mechanism activated in response to nucleolar stress.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POLYMERASE-I TRANSCRIPTION; LOCALIZATION; DISEASE; MMP-9; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III > Prof. Dr. Gernot Längst |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Apr 2020 06:04 |
| Last Modified: | 17 Apr 2020 06:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27519 |
Actions (login required)
 |
View Item |
