The E3 ligase TTC3 facilitates ubiquitination and degradation of phosphorylated Akt.

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 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 G(2)M 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.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Suizu F,Hiramuki Y,Okumura F,Matsuda M,Okumura AJ,Hirata N,Narita M,Kohno T,Yokota J,Bohgaki M,Obuse C,Hatakeyama S,Obata T,Noguchi M

doi

10.1016/j.devcel.2009.09.007

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

800-10

issue

6

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(09)00389-X

journal_volume

17

pub_type

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