DCAF7 regulates cell proliferation through IRS1-FOXO1 signaling

Scott Frendo-Cumbo; Taoyingnan Li; Dustin A. Ammendolia; Etienne Coyaud; Estelle M.N. Laurent; Yuan Liu; Philip J. Bilan; Gordon Polevoy; Brian Raught; Julie A. Brill; Amira Klip; John H. Brumell

iScience (Oct 2022)

DCAF7 regulates cell proliferation through IRS1-FOXO1 signaling

Scott Frendo-Cumbo,
Taoyingnan Li,
Dustin A. Ammendolia,
Etienne Coyaud,
Estelle M.N. Laurent,
Yuan Liu,
Philip J. Bilan,
Gordon Polevoy,
Brian Raught,
Julie A. Brill,
Amira Klip,
John H. Brumell

Affiliations

Scott Frendo-Cumbo: Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Physiology, University of Toronto, Toronto, ON M5G 1L7, Canada
Taoyingnan Li: Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada
Dustin A. Ammendolia: Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada
Etienne Coyaud: Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada
Estelle M.N. Laurent: Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada
Yuan Liu: Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
Philip J. Bilan: Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
Gordon Polevoy: Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
Brian Raught: Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada
Julie A. Brill: Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada
Amira Klip: Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Physiology, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5G 1L7, Canada
John H. Brumell: Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; SickKids IBD Centre, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Corresponding author

Journal volume & issue: Vol. 25, no. 10
p. 105188

Abstract

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Summary: Cell proliferation is dependent on growth factors insulin and IGF1. We sought to identify interactors of IRS1, the most proximal mediator of insulin/IGF1 signaling, that regulate cell proliferation. Using proximity-dependent biotin identification (BioID), we detected 40 proteins displaying proximal interactions with IRS1, including DCAF7 and its interacting partners DYRK1A and DYRK1B. In HepG2 cells, DCAF7 knockdown attenuated cell proliferation by inducing cell cycle arrest at G2. DCAF7 expression was required for insulin-stimulated AKT phosphorylation, and its absence promoted nuclear localization of the transcription factor FOXO1. DCAF7 knockdown induced expression of FOXO1-target genes implicated in G2 cell cycle inhibition, correlating with G2 cell cycle arrest. In Drosophila melanogaster, wing-specific knockdown of DCAF7/wap caused smaller wing size and lower wing cell number; the latter recovered upon double knockdown of wap and dfoxo. We propose that DCAF7 regulates cell proliferation and cell cycle via IRS1-FOXO1 signaling, of relevance to whole organism growth.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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