P73 C-terminus is dispensable for multiciliogenesis. Issue 14 (17th July 2020)

• Record Type: Journal Article
• Authors: Buckley, Niall; Panatta, Emanuele; Morone, Nobuhiro; Noguchi, Masafumi; Scorrano, Luca; Knight, Richard A.; Amelio, Ivano; Melino, Gerry
• Is Part Of: Cell cycle. Volume 19:Issue 14(2020)
• Page Start: 1833
• Page End: 1845
• Publication Date: 2020-07-17
• Subjects: P53 family -- ciliogenesis -- development; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2020.1783055
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: The p53 family transcriptional factor p73 plays a pivotal role in development. Ablation of p73 results in severe neurodevelopmental defects, chronic infections, inflammation and infertility. In addition to this, Trp73 −\- mice display severe alteration in the ciliated epithelial lining and the full-length N -terminal isoform TAp73 has been implicated in the control of multiciliogenesis transcriptional program. With our recently generated Trp73 Δ13/Δ13 mouse model, we interrogate the physiological role of p73 C-terminal isoforms in vivo . Trp73 Δ13/Δ13 mice lack exon 13 in Trp73 gene, producing an ectopic switch from the C-terminal isoforms p73α to p73β. Trp73 Δ13/Δ13 mice show a pattern of expression of TAp73 comparable to the wild-type littermates, indicating that the α to β switch does not significantly alter the expression of the gene in this cell type. Moreover, Trp73 Δ13/Δ13 do not display any significant alteration in the airway ciliated epithelium, suggesting that in this context p73β can fully substitute the function of the longer isoform p73α. Similarly, Trp73 Δ13/Δ13 ciliated epithelium of the brain ependyma also does appear defective. In this district however expression of TAp73 is not detectable, indicating that expression of the gene might be compensated by alternative mechanisms. Overall our work indicates that C-terminus p73 is dispensable for the multiciliogenesis program and suggests a possible tissue-specific effect of p73 alternative splicing.