دورية أكاديمية

RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis.

التفاصيل البيبلوغرافية
العنوان: RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis.
المؤلفون: Quiroz EJ; Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52240, USA.; Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, 90033, USA., Kim S; The Salk Institute of Biological Studies, La Jolla, CA, 92093, USA.; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, San Diego, CA, 92037, USA., Gautam LK; Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52240, USA., Borok Z; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, San Diego, CA, 92037, USA., Kintner C; The Salk Institute of Biological Studies, La Jolla, CA, 92093, USA., Ryan AL; Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52240, USA. amy-l-ryan@uiowa.edu.; Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. amy-l-ryan@uiowa.edu.; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, 90033, USA. amy-l-ryan@uiowa.edu.
المصدر: Cell death & disease [Cell Death Dis] 2024 Jan 22; Vol. 15 (1), pp. 81. Date of Electronic Publication: 2024 Jan 22.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101524092 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-4889 (Electronic) NLM ISO Abbreviation: Cell Death Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Pub. Group
مواضيع طبية MeSH: Fibroblasts* , Respiratory Tract Diseases*, Animals ; Mice ; Humans ; Cell Differentiation/genetics ; Epithelial Cells ; Epithelium ; Retinoblastoma-Like Protein p130
مستخلص: 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.
(© 2024. The Author(s).)
التعليقات: Update of: bioRxiv. 2023 Aug 04;:. (PMID: 37577572)
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معلومات مُعتمدة: R01 HL139828 United States HL NHLBI NIH HHS; R01 HL153622 United States HL NHLBI NIH HHS
المشرفين على المادة: 0 (RBL2 protein, human)
0 (Retinoblastoma-Like Protein p130)
تواريخ الأحداث: Date Created: 20240122 Date Completed: 20240124 Latest Revision: 20240205
رمز التحديث: 20240205
مُعرف محوري في PubMed: PMC10803754
DOI: 10.1038/s41419-024-06440-z
PMID: 38253523
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-4889
DOI:10.1038/s41419-024-06440-z