期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 2, 页码 340-345出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1617234114
关键词
Nat1; Eif4g1; translation control; Map3k3; mouse embryonic stem cells
资金
- Core Center for iPS Cell Research, Research Center Network for Realization of Regenerative Medicine from the Japan Agency for Medical Research and Development
- iPS Cell Research Fund
- Grants-in-Aid for Scientific Research [15K06921] Funding Source: KAKEN
Novel APOBEC1 target 1 (Nat1) (also known as p97, Dap5, and Eif4g2) is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mES cells) are resistant to differentiation. In the current study, we found that NAT1 and eIF4G1 share many binding proteins, such as the eukaryotic translation initiation factors eIF3 and eIF4A and ribosomal proteins. However, NAT1 did not bind to eIF4E or poly(A)binding proteins, which are critical for cap-dependent translation initiation. In contrast, compared with eIF4G1, NAT1 preferentially interacted with eIF2, fragile X mental retardation proteins (FMR), and related proteins and especially with members of the proline-rich and coiled-coilcontaining protein 2 (PRRC2) family. We also found that Nat1-null mES cells possess a transcriptional profile similar, although not identical, to the ground state, which is established in wild-type mES cells when treated with inhibitors of the ERK and glycogen synthase kinase 3 (GSK3) signaling pathways. In Nat1-null mES cells, the ERK pathway is suppressed evenwithout inhibitors. Ribosome profiling revealed that translation of mitogen-activated protein kinase kinase kinase 3 (Map3k3) and son of sevenless homolog 1 (Sos1) is suppressed in the absence of Nat1. Forced expression of Map3k3 induced differentiation of Nat1-nullmES cells. These data collectively show that Nat1 is involved in the translation of proteins that are required for cell differentiation.
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