CNOT3 interacts with the Aurora B and MAPK/ERK kinases to promote survival of differentiating mesendodermal progenitor cells
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Mesendoderm cells are key intermediate progenitors that form at the early primitive streak (PrS) and give rise to mesoderm and endoderm in the gastrulating embryo. We have identified an interaction between CNOT3 and the cell cycle kinase Aurora B that requires sequences in the NOT box domain of CNOT3 and regulates MAPK/ERK signaling during mesendoderm differentiation. Aurora B phosphorylates CNOT3 at two sites located close to a nuclear localization signal and promotes localization of CNOT3 to the nuclei of mouse embryonic stem cells (ESCs) and metastatic lung cancer cells. ESCs that have both sites mutated give rise to embryoid bodies that are largely devoid of mesoderm and endoderm and are composed mainly of cells with ectodermal characteristics. The mutant ESCs are also compromised in their ability to differentiate into mesendoderm in response to FGF2, BMP4, and Wnt3 due to reduced survival and proliferation of differentiating mesendoderm cells. We also show that the double mutation alters the balance of interaction of CNOT3 with Aurora B and with ERK and reduces phosphorylation of ERK in response to FGF2. Our results identify a potential adaptor function for CNOT3 that regulates the Ras/MEK/ERK pathway during embryogenesis.
Date Issued
2021-12-01
Date Acceptance
2021-10-01
Citation
Molecular Biology of the Cell, 2021, 32 (22)
ISSN
1044-2030
Publisher
American Society for Cell Biology
Journal / Book Title
Molecular Biology of the Cell
Volume
32
Issue
22
Copyright Statement
© 2021 Sarkar, Martufi, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License (https://creativecommons.org/licenses/by-nc-sa/4.0).
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Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000744541000003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
SIGNAL-REGULATED KINASE
EMBRYONIC STEM-CELLS
ERK PHOSPHORYLATION
NUCLEAR-LOCALIZATION
DEFINITIVE ENDODERM
COLORECTAL-CANCER
SCAFFOLD PROTEINS
PRIMITIVE STREAK
POOR-PROGNOSIS
MOUSE
Publication Status
Published
Article Number
ARTN ar40