Spatial consequences of blocking mTOR/S6K: Relevance for therapy

Rosner, Margit; Hengstschläger, Markus

doi:10.4161/cc.11.3.19056

Cited by 4 publications

(2 citation statements)

References 10 publications

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“…21 RPS6 is essential for ribosome biogenesis, is phosphorylated at evolutionarily conserved residues, and regulates protein synthesis, cell growth and proliferation, but also has specific features which have led to its intensive investigation as a biomarker. 22 It is most highly expressed in lymphocytes, especially naïve T cells (Figure 7). 17,18 It controls metabolic signaling in CD8 T cells; 23 has been reported to be a predictor of resistance to therapeutic inhibition of FLT3 targeting leukemic blasts; 24 and predicts sensitivity to the inhibitor of immune cell proliferation, mTOR.…”

Section: Discussionmentioning

confidence: 99%

Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis, downregulated by interferon treatment, and affected by season

et al. 2013

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Results:The MS/TCAGE association was replicated and rationalised to a single marker, ribosomal protein S6 (RPS6). Expression of RPS6 was higher in MS than controls (p<0.0004), and lower in winter than summer (p<4.6E-06). The seasonal pattern correlated with monthly UV light index (R=0.82, p<0.002), and was also identified in the BSGS cohort (p<0.0016). Variation in expression of RPS6 was not strongly heritable. RPS6 expression was reduced by IFNB therapy. Conclusions:These data support investigation of RPS6 as a potential therapeutic target and candidate biomarker for measuring clinical response to IFNB and other MS therapies, and of MS disease heterogeneity.3

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Section: Discussionmentioning

confidence: 99%

Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis, downregulated by interferon treatment, and affected by season

et al. 2013

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“…S6K1 has been mainly studied for its cytoplasmic roles because its major isoform, p70 S6K1, was incorrectly believed to localize only in the cytosol due to the lack of a nuclear localization sequence (NLS). However, several studies have shown that S6K1 is localized to the nucleus [16,17]. Our previous studies demonstrated that nuclear S6K1 inhibits the expression of three different Wnt genes and adiponectin through the direct phosphorylation of histone H2BS36 and the subsequent H3K27 trimethylation by EZH2 recruitment [18,19].…”

Section: Introductionmentioning

confidence: 98%

Nuclear S6K1 Enhances Oncogenic Wnt Signaling by Inducing Wnt/β-Catenin Transcriptional Complex Formation

Lee

Park

et al. 2022

IJMS

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Ribosomal protein S6 kinase 1 (S6K1), a key downstream effector of the mammalian target of rapamycin (mTOR), regulates diverse functions, such as cell proliferation, cell growth, and protein synthesis. Because S6K1 was previously known to be localized in the cytoplasm, its function has been mainly studied in the cytoplasm. However, the nuclear localization and function of S6K1 have recently been elucidated and other nuclear functions are expected to exist but remain elusive. Here, we show a novel nuclear role of S6K1 in regulating the expression of the Wnt target genes. Upon activation of the Wnt signaling, S6K1 translocated from the cytosol into the nucleus and subsequently bound to β-catenin and the cofactors of the Wnt/β-catenin transcriptional complex, leading to the upregulation of the Wnt target genes. The depletion or repression of S6K1 downregulated the Wnt target gene expression by inhibiting the formation of the Wnt/β-catenin transcriptional complex. The S6K1-depleted colon cancer cell lines showed lower transcription levels of the Wnt/β-catenin target genes and a decrease in the cell proliferation and invasion compared to the control cell lines. Taken together, these results indicate that nuclear S6K1 positively regulates the expression of the Wnt target genes by inducing the reciprocal interaction of the subunits of the transcriptional complex.

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Phosphorylation of nuclear and cytoplasmic pools of ribosomal protein S6 during cell cycle progression

Rosner

Hengstschläger

2012

Amino Acids

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Of all known ribosomal proteins, the 40S ribosomal protein S6 is by far the most extensively studied. Still, little is known about some basic aspects of S6 regulation including its cell cycle-related expression and localization. Using a flow cytometric single cell approach applied to whole cells and isolated nuclei, we monitored nucleocytoplasmic expression of total and S240/4 phosphorylated S6 during unperturbed cell cycle progression, providing first evidence for a S6-specific spatiotemporal pattern and its deregulation under conditions of hyperactivated mTOR.

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Spatial consequences of blocking mTOR/S6K: Relevance for therapy

Cited by 4 publications

References 10 publications

Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis, downregulated by interferon treatment, and affected by season

Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis, downregulated by interferon treatment, and affected by season

Nuclear S6K1 Enhances Oncogenic Wnt Signaling by Inducing Wnt/β-Catenin Transcriptional Complex Formation

Phosphorylation of nuclear and cytoplasmic pools of ribosomal protein S6 during cell cycle progression

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