TY - JOUR
T1 - The E3 Ligase TTC3 Facilitates Ubiquitination and Degradation of Phosphorylated Akt
AU - Suizu, Futoshi
AU - Hiramuki, Yosuke
AU - Okumura, Fumihiko
AU - Matsuda, Mami
AU - Okumura, Akiko J.
AU - Hirata, Noriyuki
AU - Narita, Masumi
AU - Kohno, Takashi
AU - Yokota, Jun
AU - Bohgaki, Miyuki
AU - Obuse, Chikashi
AU - Hatakeyama, Shigetsugu
AU - Obata, Toshiyuki
AU - Noguchi, Masayuki
N1 - Funding Information:
We thank L. Stephens, J. Chiorini, R. Kotin, T. Sato, H. Shimizu, A. Toker, J. Testa, B. Hemmings, T. Franke, R. Roth, and K. Yamamura for valuable reagents used, and A. Kojima for secretarial assistance. We also thank J. Chiorini for critically reading the manuscript. M. Noguchi and F.S. are supported by grant aid from the Japanese Ministry of Education and the Naito, Uehara, and Akiyama Foundation. We declare that we do not have any financial interest related to the work described in this manuscript.
PY - 2009/12/15
Y1 - 2009/12/15
N2 - 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 posttranslational mechanisms that modulate Akt activity remain unclear. We show here that tetratricopeptide repeat domain 3 (TTC3) is an E3 ligase that interacts with Akt. TTC3 contains a canonical RING finger motif, a pair of 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 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.
AB - 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 posttranslational mechanisms that modulate Akt activity remain unclear. We show here that tetratricopeptide repeat domain 3 (TTC3) is an E3 ligase that interacts with Akt. TTC3 contains a canonical RING finger motif, a pair of 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 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.
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U2 - 10.1016/j.devcel.2009.09.007
DO - 10.1016/j.devcel.2009.09.007
M3 - Article
C2 - 20059950
AN - SCOPUS:71649104466
SN - 1534-5807
VL - 17
SP - 800
EP - 810
JO - Developmental Cell
JF - Developmental Cell
IS - 6
ER -
