RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis.

Autor:	Quiroz EJ; Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52240.; Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA 90033.; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033., Kim S; The Salk Institute of Biological Studies, La Jolla, CA 92093.; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, San Diego, CA 92037., Gautam LK; Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52240., Borok Z; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, San Diego, CA 92037., Kintner C; The Salk Institute of Biological Studies, La Jolla, CA 92093., Ryan AL; Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52240.; Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA 90033.; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Aug 04. Date of Electronic Publication: 2023 Aug 04.
DOI:	10.1101/2023.08.04.551992
Abstrakt:	A core pathophysiologic feature underlying many respiratory diseases is multiciliated cell dysfunction, leading to inadequate mucociliary clearance. Due to the prevalence and highly variable etiology of mucociliary dysfunction in respiratory diseases, it is critical to understand the mechanisms controlling multiciliogenesis that may be targeted to restore functional mucociliary clearance. Multicilin, in a complex with E2F4, is necessary and sufficient to drive multiciliogenesis in airway epithelia, however this does not apply to all cell types, nor does it occur evenly across all cells in the same cell population. In this study we further investigated how co-factors regulate the ability of Multicilin to drive multiciliogenesis. Combining data in mouse embryonic fibroblasts and human bronchial epithelial cells, we identify RBL2 as a repressor of the transcriptional activity of Multicilin. Knockdown of RBL2 in submerged cultures or phosphorylation of RBL2 in response to apical air exposure, in the presence of Multicilin, allows multiciliogenesis to progress. These data demonstrate a dynamic interaction between RBL2 and Multicilin that regulates the capacity of cells to differentiate and multiciliate. Identification of this mechanism has important implications for facilitating MCC differentiation in diseases with impaired mucociliary clearance. Competing Interests: Declaration of interests The authors have declared that no conflicts of interest exist.
Databáze:	MEDLINE
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