The Rps6kb1 gene encodes the 70 kDa ribosomal protein S6 kinase (p70S6K), which is a serine/threonine kinase regulated by phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway. p70S6K plays a crucial role in controlling cell cycle, growth and survival. The PI3K/mTOR signalling pathway is one of the major mechanisms for controlling cell survival, proliferation and metabolism and is the central regulator of translation of some components of protein synthesis system. Upon activation, this kinase phosphorylates S6 protein of ribosomal subunit 40S resulting in selective translation of unique family of mRNAs that contain oligopyrimidine tract on 5' transcriptional site (5'TOP). 5'TOP mRNAs are coding the components of translational apparatus including ribosomal proteins and elongation factors. Due to the role of p70S6K in protein synthesis and also its involvement in a variety of human diseases ranging from diabetes and obesity to cancer, p70S6K is now being considered as a new therapeutic target for drug development. Furthermore, p70S6K acts as a biomarker for response to immunosuppressant as well as anticancer effects of inhibitors of the mTOR. Because of the narrow therapeutic index of mTOR inhibitors, drug monitoring is essential, and this is usually done by measuring blood drug levels, therapeutic response and drug-induced adverse effects. Recent studies have suggested that plasma p70S6K is a reliable index for the monitoring of patient response to mTOR inhibitors. Therefore, a better understanding of p70S6K and its role in various pathological conditions could enable the development of strategies to aid diagnosis, prognosis and treatment schedules.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1136/jclinpath-2014-202560 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
UBA52 Mediates ribosomal DNA stability under hexavalent chromium exposure in occupational workers and cellular models.
Ecotoxicol Environ Saf
March 2025
School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang 310013, China; Huzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, School of Medicine, and the First Affiliated Hospital, Huzhou University, Huzhou, Zhejiang 313000, China. Electronic address:
Hexavalent chromium [Cr(VI)] exposure poses substantial environmental and health risks, especially in occupational settings, where it has been linked to genomic instability. Our previous research demonstrated that Cr(VI) exposure could induce DNA copy number (CN) variation. Here, we examined the role of Ubiquitin A-52 ribosomal protein fusion product 1 (UBA52) in stabilizing rDNA CN under Cr(VI) exposure by analyzing data from Cr(VI)-exposed workers and matched controls.
View Article and Find Full Text PDFProteostasis Disruption in Inherited Bone Marrow Failure Syndromes.
Blood
March 2025
UC San Diego, La Jolla, California, United States.
Inherited bone marrow failure syndromes (IBMFS) are genetic disorders of impaired hematopoiesis that manifest in childhood with both cytopenias and extra-hematologic findings. While several IBMFS are categorized as ribosomopathies due to shared underlying ribosomal dysfunction, there is a broader disruption of the protein homeostasis (proteostasis) network across both classic and emerging IBMFS. Precise regulation of the proteostasis network, including mechanisms of protein synthesis, folding, trafficking, and degradation as well as associated stress response pathways, has emerged as essential for maintaining hematopoietic stem cell (HSC) function, providing new potential mechanistic insights into IBMFS pathogenesis.
View Article and Find Full Text PDFShank3 modulates Rpl3 expression and protein synthesis via mGlu5: implications for Phelan McDermid syndrome.
Mol Psychiatry
March 2025
CNR, Neuroscience Institute, Milano, Italy.
Mutations or deletions in the SHANK3 gene have been identified in up to 1% of autism spectrum disorder cases and are considered the primary cause of neuropsychiatric symptoms in Phelan McDermid syndrome (PMS). While synaptic dysfunctions have been extensively documented in the absence of Shank3, other mechanisms through which Shank3 may regulate neuronal functions remain unclear. In this study, we report that the ribosomal protein Rpl3 and overall protein synthesis are downregulated in the cortex and striatum of Shank3 knockout (KO) mice and in neurons differentiated from human-induced pluripotent stem cells (hiPSCs) derived from a PMS patient.
View Article and Find Full Text PDFPRC1 promotes ovarian cancer progression by binding to RPL4 and increasing MDM2-mediated p53 ubiquitination.
Exp Cell Res
March 2025
Department of Gynecological Oncology, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China. Electronic address:
Ovarian cancer (OC) is one of the most fatal gynecological carcinomas, causing significant detriment to women's health. Protein regulator of cytokinesis 1 (PRC1) is a microtubule-associated protein that is found to be highly expressed in many different cancers. Despite this, the exact way in which PRC1 stimulates the growth of OC has yet to be completely understood.
View Article and Find Full Text PDFSpecific enhancement of the translation of thermospermine-responsive uORF-containing mRNAs by ribosomal mutations in .
Plant Signal Behav
December 2025
Graduate School of Environmental, Life, Natural Science and Technology, Okayama University, Okayama, Japan.
Auxin-induced xylem formation in angiosperms is negatively regulated by thermospermine, whose biosynthesis is also induced by auxin. In , loss-of-function mutants of , which encodes thermospermine synthase, exhibit a dwarf phenotype accompanied by excessive xylem formation. Studies of suppressor mutants that recover from the dwarf phenotype suggest that thermospermine alleviates the inhibitory effect of an upstream open-reading frame (uORF) on the main ORF translation of mRNA.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!