Published in

Elsevier, International Review of Cell and Molecular Biology, p. 181-229, 2016

DOI: 10.1016/bs.ircmb.2015.12.007

Links

Tools

Export citation

Search in Google Scholar

New Insights Into the Mechanism of COP9 Signalosome-Cullin-RING Ubiquitin-Ligase Pathway Deregulation in Urological Cancers

This paper is available in a repository.
This paper is available in a repository.

Full text: Download

Green circle
Preprint: archiving allowed
Red circle
Postprint: archiving forbidden
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

Abstract

Urological cancers are a very common type of cancer worldwide and have alarming high incidence and mortality rates, especially in kidney cancers, illustrate the urgent need for new therapeutic targets. Recent publications point to a deregulated COP9 signalosome (CSN)-cullin-RING ubiquitin-ligase (CRL) pathway which is here considered and investigated as potential target in urological cancers with strong focus on renal cell carcinomas (RCC). The CSN forms supercomplexes with CRLs in order to preserve protein homeostasis and was found deregulated in several cancer types. Examination of selected CSN-CRL pathway components in RCC patient samples and four RCC cell lines revealed an interesting deregulated p27Kip1-Skp2-CAND1 axis and two p27Kip1 point mutations in 786-O cells; p27Kip1V109G and p27Kip1I119T. The p27Kip1 mutants were detected in patients with RCC and appear to be responsible for an accelerated growth rate in 786-O cells. The occurrence of p27Kip1V109G and p27Kip1I119T in RCC makes the CSN-CRL pathway an attractive therapeutic target.