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BAD regulates mammary gland morphogenesis by 4E-BP1-mediated control of localized translation in mouse and human models.
Githaka, John Maringa; Tripathi, Namita; Kirschenman, Raven; Patel, Namrata; Pandya, Vrajesh; Kramer, David A; Montpetit, Rachel; Zhu, Lin Fu; Sonenberg, Nahum; Fahlman, Richard P; Danial, Nika N; Underhill, D Alan; Goping, Ing Swie.
Afiliação
  • Githaka JM; Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
  • Tripathi N; Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
  • Kirschenman R; Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
  • Patel N; Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
  • Pandya V; Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
  • Kramer DA; Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
  • Montpetit R; Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
  • Zhu LF; Department of Surgery, University of Alberta, Edmonton, AB, Canada.
  • Sonenberg N; Department of Biochemistry, McGill University, Montreal, QC, Canada.
  • Fahlman RP; Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
  • Danial NN; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Underhill DA; Department of Oncology, University of Alberta, Edmonton, AB, Canada.
  • Goping IS; Department of Biochemistry, University of Alberta, Edmonton, AB, Canada. igoping@ualberta.ca.
Nat Commun ; 12(1): 2939, 2021 05 19.
Article em En | MEDLINE | ID: mdl-34011960
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas de Ciclo Celular / Glândulas Mamárias Humanas / Proteínas Adaptadoras de Transdução de Sinal / Proteína de Morte Celular Associada a bcl / Glândulas Mamárias Animais Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas de Ciclo Celular / Glândulas Mamárias Humanas / Proteínas Adaptadoras de Transdução de Sinal / Proteína de Morte Celular Associada a bcl / Glândulas Mamárias Animais Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article