Oncotarget

Research Papers:

PIM1 destabilization activates a p53-dependent response to ribosomal stress in cancer cells

Vinay Sagar _, Sara Caldarola, Valentina Aria, Valentina Monteleone, Claudia Fuoco, Cesare Gargioli, Stefano Cannata and Fabrizio Loreni

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:23837-23849. https://doi.org/10.18632/oncotarget.8070

Metrics: PDF 934 views  |   HTML 1144 views  |   ?  


Abstract

Vinay Sagar1, Sara Caldarola1, Valentina Aria1, Valentina Monteleone1, Claudia Fuoco1, Cesare Gargioli1, Stefano Cannata1, Fabrizio Loreni1

1Department of Biology, University of Rome Tor Vergata, Roma, Italy

Correspondence to:

Fabrizio Loreni, email: loreni@uniroma2.it

Keywords: PIM1, MDM2, AKT, p53, ribosomal stress

Received: November 03, 2015     Accepted: February 29, 2016     Published: March 14, 2016

ABSTRACT

Defects in ribosome biogenesis triggers a stress response (ribosomal stress) that can lead to growth arrest and apoptosis. Signaling pathways activated by ribosomal stress are specifically involved in the pathological mechanism of a group of disorders defined as ribosomopathies. However, more generally, the quality control of ribosome synthesis is part of the regulatory circuits that control cell metabolism. A number of studies identified tumor suppressor p53 as a central player in ribosomal stress. We have previously reported that the kinase PIM1 plays a role as a sensor for ribosome deficiency. In this report we address the relationship between PIM1 and p53 in cancer cell lines after depletion of a ribosomal protein. We identified a novel signaling pathway that includes the kinase AKT and the ubiquitin ligase MDM2. In fact, our results indicate that the lower level of PIM1, induced by ribosomal stress, causes inactivation of AKT, inhibition of MDM2 and a consequent p53 stabilization. Therefore, we propose that activation of p53 in response to ribosomal stress, is dependent on the pathway PIM1-AKT-MDM2. In addition, we report evidence that PIM1 level may be relevant to assess the sensitivity of cancer cells to chemotherapeutic drugs that induce ribosomal stress.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 8070