Phosphorylation of Right Open Reading Frame 2 (Rio2) Protein Kinase by Polo-like Kinase 1 Regulates Mitotic Progression

Liu, Ting; Deng, Min; Li, Junhui; Qian, Wei; Ye, Xin

doi:10.1074/jbc.m111.250175

Cited by 28 publications

(36 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RIOK2 has several putative and mapped phosphorylation sites, including at least one putative Akt phosphorylation site (www.phosphosite.org, Figure S8). Other studies show that RIOK2 phosphorylation can be stimulated by EGFR, and can be carried out by Polo-like kinase 1 [21], [61], and perhaps these events contribute to Akt-mediated regulation of RIO kinase levels. Of note, though standard GBM cells lacking PTEN showed high levels of RIO kinase expression, non-transformed astrocytes lacking PTEN did not show high levels of endogenous RIO kinase protein expression relative to astrocytes with intact PTEN.…”

Section: Discussionmentioning

confidence: 95%

A Kinome-Wide RNAi Screen in Drosophila Glia Reveals That the RIO Kinases Mediate Cell Proliferation and Survival through TORC2-Akt Signaling in Glioblastoma

et al. 2013

View full text Add to dashboard Cite

Glioblastoma, the most common primary malignant brain tumor, is incurable with current therapies. Genetic and molecular analyses demonstrate that glioblastomas frequently display mutations that activate receptor tyrosine kinase (RTK) and Pi-3 kinase (PI3K) signaling pathways. In Drosophila melanogaster, activation of RTK and PI3K pathways in glial progenitor cells creates malignant neoplastic glial tumors that display many features of human glioblastoma. In both human and Drosophila, activation of the RTK and PI3K pathways stimulates Akt signaling along with other as-yet-unknown changes that drive oncogenesis. We used this Drosophila glioblastoma model to perform a kinome-wide genetic screen for new genes required for RTK- and PI3K-dependent neoplastic transformation. Human orthologs of novel kinases uncovered by these screens were functionally assessed in mammalian glioblastoma models and human tumors. Our results revealed that the atypical kinases RIOK1 and RIOK2 are overexpressed in glioblastoma cells in an Akt-dependent manner. Moreover, we found that overexpressed RIOK2 formed a complex with RIOK1, mTor, and mTor-complex-2 components, and that overexpressed RIOK2 upregulated Akt signaling and promoted tumorigenesis in murine astrocytes. Conversely, reduced expression of RIOK1 or RIOK2 disrupted Akt signaling and caused cell cycle exit, apoptosis, and chemosensitivity in glioblastoma cells by inducing p53 activity through the RpL11-dependent ribosomal stress checkpoint. These results imply that, in glioblastoma cells, constitutive Akt signaling drives RIO kinase overexpression, which creates a feedforward loop that promotes and maintains oncogenic Akt activity through stimulation of mTor signaling. Further study of the RIO kinases as well as other kinases identified in our Drosophila screen may reveal new insights into defects underlying glioblastoma and related cancers and may reveal new therapeutic opportunities for these cancers.

show abstract

Section: Discussionmentioning

confidence: 95%

A Kinome-Wide RNAi Screen in Drosophila Glia Reveals That the RIO Kinases Mediate Cell Proliferation and Survival through TORC2-Akt Signaling in Glioblastoma

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Knockdown of RIOK1 arrests yeast cells at S and mitosis phases 7 . RIOK2 acts as the substrate of PLK1 and is required for the proper mitotic progression in Hela cells 8 . In addition, our recent work has found that down‐regulation of RIOK3 causes G1 arrest, whereas overexpression of RIOK3 accelerates cell cycle progression in glioma cells 9 .…”

Section: Introductionmentioning

confidence: 99%

RIOK2 is negatively regulated by miR‐4744 and promotes glioma cell migration/invasion through epithelial‐mesenchymal transition

Song

Cheng

Jin

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

RIOK2 is a member of RIO (right open reading frame) kinase family. Recent studies have revealed the involvement of RIO kinases in glioma cell growth and expansion. However, the role and mechanism of RIOK2 in glioma cell migration and invasion remain unclear. Wound healing assay, Transwell assay and real-time quantitative PCR (qRT-PCR) detection of matrix metalloproteinases (MMPs) were used to evaluate the migration/invasion of glioma cells. Western blot and qRT-PCR were employed to measure the expression of epithelial-mesenchymal transition (EMT) markers. Dual luciferase reporter assay was performed to determine the binding between RIOK2 and miR-4744. In addition, RIOK2 and miR-4744 levels were quantified by qRT-PCR and/ or immunohistochemistry in glioma tissues. Transfection of RIOK2 siRNAs significantly inhibited glioma cell migration and invasion and down-regulated the expression of MMPs (MMP2 and MMP9) and mesenchymal markers (N-cadherin, β-catenin, Twist1, fibronectin, ZEB-1) in glioma cells. Overexpression of RIOK2 showed the opposite effects. MiR-4744 directly bound to the 3'-untranslated region of RIOK2 and negatively regulated the expression of RIOK2. Up-regulation of miR-4744 inhibited the migration and invasion of glioma cells. Overexpression of RIOK2 could reverse the effects of miR-4744 up-regulation on the migration, invasion and EMT process in glioma cells. Moreover, RIOK2 was high, while miR-4744 was low in glioma tissues, and a negative correlation was found between them. These results suggest that RIOK2 is post-transcriptionally targeted by miR-4744, the low miR-4744 and high RIOK2 levels in glioma may contribute to tumour cell infiltration through promoting the EMT. K E Y W O R D S fibronectin, glioma, miR-4744, N-cadherin, RIOK2, β-catenin | 4495 SONG et al. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Song Y, Li C, Jin L, et al. RIOK2 is negatively regulated by miR-4744 and promotes glioma cell migration/invasion through epithelial-mesenchymal transition.

show abstract

“…To determine which region of Plk1 is required for its interaction with P-TEFb, pCMV FLAG-Plk1(1-330) and pCMV FLAG-Plk1(330-603) were generated as described previously [23] (Figure 2A) and transfected into 293T cells. The data from immunoprecipitation demonstrated that the C-terminal polo-box domains of Plk1 are mainly responsible for its binding with P-TEFb complex, while its N-terminal region shows very weak interaction with P-TEFb.…”

Section: Resultsmentioning

confidence: 99%

“…pCMV FLAG-Plk1 and its mutants and bacteria expression plasmids pET-30a-Plk1, pET-30a-Plk1 TD (constitutively active form of Plk1) and pET-30a-Plk1 KD (kinase deficient form of Plk1) were generated as described previously [23]. pCMV myc-Plk1 were made by cloning Plk1 cDNA into the pCMV myc vector (BD Clontech) at EcoRI-XhoI sites.…”

Section: Methodsmentioning

confidence: 99%

Polo-Like Kinase 1 Inhibits the Activity of Positive Transcription Elongation Factor of RNA Pol II b (P-TEFb)

et al. 2013

Self Cite

View full text Add to dashboard Cite

Polo-like kinase 1 (Plk1) is a highly conserved Ser/Thr kinase in eukaryotes and plays a critical role in various aspects of the cell cycle. Plk1 exerts its multiple functions by phosphorylating its substrates. In this study, we found that Plk1 can interact with cyclin T1/Cdk9 complex-the main form of the positive transcription elongation complex b (P-TEFb), and its C-terminal polo-box domain is responsible for the binding. Further analysis indicated that Plk1 could phosphorylate cyclin T1 at Ser564 and inhibit the kinase activity of cyclin T1/Cdk9 complex on phosphorylation of the C-terminal domain (CTD) of RNA polymerase II. By taking the approach of luciferase assay, we demonstrated that over-expression of both wild type Plk1 and constitutively active form of Plk1 inhibits the P-TEFb dependent HIV-1 LTR transcription, while knockdown of Plk1 increases the HIV-1 LTR transcription. Consistently, the data from the HIV-1 pseudovirus reporter assay indicated that Plk1 blocks the gene expression of HIV-1 pseudovirus. Taken together, our results revealed that Plk1 negatively regulates the RNA polymerase II-dependent transcription through inhibiting the activity of cyclin T1/Cdk9 complex.

show abstract

Phosphorylation of Right Open Reading Frame 2 (Rio2) Protein Kinase by Polo-like Kinase 1 Regulates Mitotic Progression

Cited by 28 publications

References 36 publications

A Kinome-Wide RNAi Screen in Drosophila Glia Reveals That the RIO Kinases Mediate Cell Proliferation and Survival through TORC2-Akt Signaling in Glioblastoma

A Kinome-Wide RNAi Screen in Drosophila Glia Reveals That the RIO Kinases Mediate Cell Proliferation and Survival through TORC2-Akt Signaling in Glioblastoma

RIOK2 is negatively regulated by miR‐4744 and promotes glioma cell migration/invasion through epithelial‐mesenchymal transition

Polo-Like Kinase 1 Inhibits the Activity of Positive Transcription Elongation Factor of RNA Pol II b (P-TEFb)

Contact Info

Product

Resources

About