The ubiquitin-proteasome system in glioma cell cycle control

Panagiotis J Vlachostergios,Ioannis A Voutsadakis,Christos N Papandreou

doi:10.1186/1747-1028-7-18

Panagiotis J Vlachostergios, Ioannis A Voutsadakis + Show 1 more

Open Access

https://doi.org/10.1186/1747-1028-7-18

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Abstract

A major determinant of cell fate is regulation of cell cycle. Tight regulation of this process is lost during the course of development and progression of various tumors. The ubiquitin-proteasome system (UPS) constitutes a universal protein degradation pathway, essential for the consistent recycling of a plethora of proteins with distinct structural and functional roles within the cell, including cell cycle regulation. High grade tumors, such as glioblastomas have an inherent potential of escaping cell cycle control mechanisms and are often refractory to conventional treatment. Here, we review the association of UPS with several UPS-targeted proteins and pathways involved in regulation of the cell cycle in malignant gliomas, and discuss the potential role of UPS inhibitors in reinstitution of cell cycle control.

Highlights

Malignant gliomas constitute a spectrum of poorly differentiated primary brain tumors of astrocytic or oligodendroglial origin with a marked resistance to treatment, a high tendency of recurrence and a poor prognosis [1,2].Deregulation of cell cycle in most cancer cell types, including glioma is a critical mechanism of development, progression, and resistance to treatment [3]
The ubiquitin-proteasome system (UPS) is longknown as a cellular tool for the marking and proteolytic degradation of proteins involved in a wide variety of structural and functional roles inside the cell
The E2F1 protein, a cellular mediator involved in the transition from G1 to S phase was found to be degraded by the proteasome in response to Δ9-tetrahydrocannabinol treatment of human GBM cells, blocking cell cycle progression and supporting a role for cannabinoids as anticancer agents [23]

Summary

Introduction

Malignant gliomas constitute a spectrum of poorly differentiated primary brain tumors of astrocytic or oligodendroglial origin with a marked resistance to treatment, a high tendency of recurrence and a poor prognosis [1,2].Deregulation of cell cycle in most cancer cell types, including glioma is a critical mechanism of development, progression, and resistance to treatment [3]. A great number of cellular proteins with various roles, including cell cycle control, either comprise direct targets of an aberrant degradation machinery or have a close structural or/and functional connection with abnormal ubiquitin- or ubiquitin like-ligases, deubiquitinating enzymes and UPS-regulated signaling factors and pathways [6,7,8].

Results

Conclusion