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Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathways

Open access
Gan, Boyi, Peng, Xu, Nagy, Tamas, Alcaraz, Ana, Gu, Hua, Guan, Jun-Lin·2006·The Journal of Cell Biology

Abstract

Focal adhesion kinase family interacting protein of 200 kD (FIP200) has been shown to regulate diverse cellular functions such as cell size, proliferation, and migration in vitro. However, the function of FIP200 in vivo has not been investigated. We show that targeted deletion of FIP200 in the mouse led to embryonic death at mid/late gestation associated with heart failure and liver degeneration. We found that FIP200 knockout (KO) embryos show reduced S6 kinase activation and cell size as a result of increased tuberous sclerosis complex function. Furthermore, FIP200 KO embryos exhibited significant apoptosis in heart and liver. Consistent with this, FIP200 KO mouse embryo fibroblasts and liver cells showed increased apoptosis and reduced c-Jun N-terminal kinase phosphorylation in response to tumor necrosis factor (TNF) α stimulation, which might be mediated by FIP200 interaction with apoptosis signal–regulating kinase 1 (ASK1) and TNF receptor–associated factor 2 (TRAF2), regulation of TRAF2–ASK1 interaction, and ASK1 phosphorylation. Together, our results reveal that FIP200 functions as a regulatory node to couple two important signaling pathways to regulate cell growth and survival during mouse embryogenesis.

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Metadata

Authors
Gan, B., Peng, X., Nagy, T., Alcaraz, A., Gu, H., & Guan, J.-L.
Venue
The Journal of Cell Biology
Published
2006-10-02
Volume
175
Issue
1
Pages
121-133
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
OpenAlex
W2019713643
Cited by
230
References
8
FWCI
1.60
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathways. https://app.cochat.ai/papers/10.1083/jcb.200604129
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Gan, B., Peng, X., Nagy, T., Alcaraz, A., Gu, H., & Guan, J.-L. (2006). Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathways. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200604129

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