| Literature DB >> 34011960 |
John Maringa Githaka1, Namita Tripathi1, Raven Kirschenman1, Namrata Patel1, Vrajesh Pandya1, David A Kramer1, Rachel Montpetit1, Lin Fu Zhu2, Nahum Sonenberg3, Richard P Fahlman1, Nika N Danial4, D Alan Underhill5, Ing Swie Goping6,7.
Abstract
Elucidation of non-canonical protein functions can identify novel tissue homeostasis pathways. Herein, we describe a role for the Bcl-2 family member BAD in postnatal mammary gland morphogenesis. In Bad3SA knock-in mice, where BAD cannot undergo phosphorylation at 3 key serine residues, pubertal gland development is delayed due to aberrant tubulogenesis of the ductal epithelium. Proteomic and RPPA analyses identify that BAD regulates focal adhesions and the mRNA translation repressor, 4E-BP1. These results suggest that BAD modulates localized translation that drives focal adhesion maturation and cell motility. Consistent with this, cells within Bad3SA organoids contain unstable protrusions with decreased compartmentalized mRNA translation and focal adhesions, and exhibit reduced cell migration and tubulogenesis. Critically, protrusion stability is rescued by 4E-BP1 depletion. Together our results confirm an unexpected role of BAD in controlling localized translation and cell migration during mammary gland development.Entities:
Year: 2021 PMID： 34011960 DOI： 10.1038/s41467-021-23269-8
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919