The COP9 signalosome subunit 6 (CSN6): a potential oncogene

Shang-Nuan Zhang,Dong-Sheng Pei,Jun-Nian Zheng

doi:10.1186/1747-1028-8-14

Abstract

CSN6 is one subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), which is an evolutionarily conserved multiprotein complex found in plants and animals and originally described as a repressor of light-dependent growth and transcription in Arabidopsis. CSN is homologous to the 19S lid subcomplex of the 26S proteasome, thus it has been postulated to be a regulator of the ubiquitin-proteasome pathway. In mammalian cells, it consists of eight subunits (CSN1-CSN8). Among the CSN subunits, CSN5 and CSN6 are the only two that each contains an MPN (Mpr1p and Pad1p N-terminal) domain. The deneddylating activity of an MPN domain toward cullin-RING ubiquitin ligases (CRL) may coordinate CRL-mediated ubiquitination activity. More and more studies about CSN6 are emerging, and its overexpression is found in many types of cancers. Evidence has shown that CSN6 is a molecule platform between protein degradation and signal transduction. Here, we provide a summary of human CSN6, especially its roles in cancer, hoping that it can lay the groundwork for cancer prevention or therapy.

Highlights

The constitutive photomorphogenesis 9 (COP9) signalosome, generally named CSN, is an evolutionarily conserved multiprotein complex existing in all eukaryotes
Loss of expression of CSN6 could attenuate carcinogenesis/tumor progression in response to DNA damage, which is known to be impeded by p53. These results suggest that CSN6 is an oncogene with positive activity toward MDM2 and plays a significant role in DNA damage-associated apoptosis and tumorigenesis through MDM2-p53 signaling pathway
As a subunit of COP9 signalosome, the roles of CSN6 in cancer could be linked to its involvement in ubiquitin-mediated protein degradation

Summary

Introduction

The COP9 signalosome, generally named CSN, is an evolutionarily conserved multiprotein complex existing in all eukaryotes. The most and best studied function is regulation of ubiquitin-mediated protein degradation [10,11,12,13]. Since many key oncogene and tumor suppressor products such as p27 [18], c-Jun [19], p53 [8,20,21], COP1 [22] and 14-3-3σ [22] are degraded via the ubiquitin-proteasome pathway, it is conceivable that COP9 plays a significant role in cancer.

Results

Conclusion