Title: | The E3 Ligase TTC3 Facilitates Ubiquitination and Degradation of Phosphorylated Akt |
Authors: | Suizu, Futoshi Browse this author →KAKEN DB |
Hiramuki, Yosuke Browse this author |
Okumura, Fumihiko Browse this author |
Matsuda, Mami Browse this author |
Okumura, Akiko J. Browse this author |
Hirata, Noriyuki Browse this author |
Narita, Masumi Browse this author |
Kohno, Takashi Browse this author |
Yokota, Jun Browse this author |
Bohgaki, Miyuki Browse this author |
Obuse, Chikashi Browse this author |
Hatakeyama, Shigetsugu Browse this author →KAKEN DB |
Obata, Toshiyuki Browse this author |
Noguchi, Masayuki Browse this author →KAKEN DB |
Keywords: | Akt |
ubiquitin ligase |
phosphorylation |
signal transduction |
Issue Date: | Dec-2009 |
Publisher: | Elsevier |
Journal Title: | Developmental Cell |
Volume: | 17 |
Issue: | 6 |
Start Page: | 800 |
End Page: | 810 |
Publisher DOI: | 10.1016/j.devcel.2009.09.007 |
PMID: | 20059950 |
Abstract: | The serine threonine kinase Akt is a core survival factor that underlies a variety of human diseases. Although regulatory phosphorylation and dephosphorylation have been well documented, the other post-translational mechanisms that modulate Akt activity remain unclear. We show herein that TTC3 (tetratricopeptide repeat domain 3) is an E3 ligase that interacts with Akt. TTC3 contains a canonical RING-finger motif, a pair of TPR (tetratricopeptide) motifs, a putative Akt phosphorylation site, and nuclear localization signals, and is encoded by a gene within the Down Syndrome (DS) Critical Region on chromosome 21. TTC3 is an Akt-specific specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. Moreover, DS cells exhibit elevated TTC3 expression, reduced phosphorylated Akt, and accumulation in the G2M phase, which can be reversed by TTC3 siRNA or Myr-Akt. Thus, interaction between TTC3 and Akt may contribute to the clinical symptoms of DS. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/54768 |
Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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