Dataset Information

P70S6K1 (S6K1)-mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I ? Degradation and Cell Invasion.

ABSTRACT: Phosphatidylinositol 4-phosphate 5-kinase type I ? (PIPKI?90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration, and invasion. However, it is unknown how upstream signals control PIPKI?90 ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKI?90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKI?90 phosphorylation is essential for cell migration and invasion. Moreover, PIPKI?90 phosphorylation is required for the development of focal adhesions and invadopodia, key machineries for cell migration and invasion. Surprisingly, substitution of Thr-553 and Ser-555 with Ala promoted PIPKI?90 ubiquitination but enhanced the stability of PIPKI?90, and depletion of S6K1 also enhanced the stability of PIPKI?90, indicating that PIPKI?90 ubiquitination alone is insufficient for its degradation. These data suggest that S6K1-mediated PIPKI?90 phosphorylation regulates cell migration and invasion by controlling PIPKI?90 degradation.

SUBMITTER: Jafari N

PROVIDER: S-EPMC5207268 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

p70S6K1 (S6K1)-mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I γ Degradation and Cell Invasion.

Jafari Naser N Zheng Qiaodan Q Li Liqing L Li Wei W Qi Lei L Xiao Jianyong J Gao Tianyan T Huang Cai C

The Journal of biological chemistry 20161025 49

Phosphatidylinositol 4-phosphate 5-kinase type I γ (PIPKIγ90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration, and invasion. However, it is unknown how upstream signals control PIPKIγ90 ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. Mo ...[more]

PMID: 27780861

Similar Datasets

Project description:The lipid kinase phosphatidylinositol 4-kinase III alpha (PI4KIII?) is an essential host factor of hepatitis C virus (HCV) replication. PI4KIII? catalyzes the synthesis of phosphatidylinositol 4-phosphate (PI4P) accumulating in HCV replicating cells due to enzyme activation resulting from its interaction with nonstructural protein 5A (NS5A). This study describes the interaction between PI4KIII? and NS5A and its mechanistic role in viral RNA replication. We mapped the NS5A sequence involved in PI4KIII? interaction to the carboxyterminal end of domain 1 and identified a highly conserved PI4KIII? functional interaction site (PFIS) encompassing seven amino acids, which are essential for viral RNA replication. Mutations within this region were also impaired in NS5A-PI4KIII? binding, reduced PI4P levels and altered the morphology of viral replication sites, reminiscent to the phenotype observed by silencing of PI4KIII?. Interestingly, abrogation of RNA replication caused by mutations in the PFIS correlated with increased levels of hyperphosphorylated NS5A (p58), indicating that PI4KIII? affects the phosphorylation status of NS5A. RNAi-mediated knockdown of PI4KIII? or pharmacological ablation of kinase activity led to a relative increase of p58. In contrast, overexpression of enzymatically active PI4KIII? increased relative abundance of basally phosphorylated NS5A (p56). PI4KIII? therefore regulates the phosphorylation status of NS5A and viral RNA replication by favoring p56 or repressing p58 synthesis. Replication deficiencies of PFIS mutants in NS5A could not be rescued by increasing PI4P levels, but by supplying functional NS5A, supporting an essential role of PI4KIII? in HCV replication regulating NS5A phosphorylation, thereby modulating the morphology of viral replication sites. In conclusion, we demonstrate that PI4KIII? activity affects the NS5A phosphorylation status. Our results highlight the importance of PI4KIII? in the morphogenesis of viral replication sites and its regulation by facilitating p56 synthesis.

Dataset Information

P70S6K1 (S6K1)-mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I ? Degradation and Cell Invasion.

Publications

p70S6K1 (S6K1)-mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I γ Degradation and Cell Invasion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure