Overexpression and poly-ubiquitylation of the DEAD-box RNA helicase p68 incolorectal tumours

The DEAD box RNA helicase, p68, is upregulated in exponentially growing cel ls and shows cell cycle-dependent changes in nuclear localization. Although some other DEAD box proteins have been implicated in cancer, there have be en no reports of any link between p68 status and carcinogenesis. In the pre sent study we have analysed specimens from 50 patients with colorectal aden ocarcinomas, including cases in which an adenomatous polyp was also present , by immunohistochemistry and Western blotting. Our data indicate that p68 protein is consistently overexpressed in tumours as compared with matched n ormal tissue. Examination of the levels of p68 mRNA from both normal and tu mour tissue showed no obvious specific increase in p68 mRNA levels in tumou rs nor any evidence of underlying mutations in the p68 coding region. Inter estingly, however, the accumulated p68 appears to be poly-ubiquitylated, su ggesting a possible defect in proteasome-mediated degradation in these tumo urs. This overexpression/ubiquitylation is observed in both pre-invasive an d invasive lesions suggesting that the dysregulation of p68 expression occu rs early during tumour development. Finally, we demonstrate that ubiquityla tion of p68 occurs in cultured cells, thereby providing a model for the mol ecular analysis of this process and its potential role in tumorigenesis.