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

TY - JOUR

T1 - Overexpression and poly-ubiquitylation of the DEAD-box RNA helicase p68 in colorectal tumours

AU - Causevic, Mirsada

AU - Hislop, R. Gordon

AU - Kernohan, Neil M.

AU - Carey, Francis A.

AU - Kay, Richard A.

AU - Steele, Robert J. C.

AU - Fuller-Pace, Frances V.

N1 - dc.publisher: Nature Publishing Group dc.description.sponsorship: Medical Research Council (UK) Association for International Cancer Research Chief Scientist's Office of the Scottish Executive Health Department

PY - 2001/11

Y1 - 2001/11

N2 - The DEAD box RNA helicase, p68, is upregulated in exponentially growing cells and shows cell cycle-dependent changes in nuclear localization. Although some other DEAD box proteins have been implicated in cancer, there have been no reports of any link between p68 status and carcinogenesis. In the present study we have analysed specimens from 50 patients with colorectal adenocarcinomas, 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 normal tissue. Examination of the levels of p68 mRNA from both normal and tumour tissue showed no obvious specific increase in p68 mRNA levels in tumours nor any evidence of underlying mutations in the p68 coding region. Interestingly, however, the accumulated p68 appears to be poly-ubiquitylated, suggesting a possible defect in proteasome-mediated degradation in these tumours. This overexpression/ubiquitylation is observed in both pre-invasive and invasive lesions suggesting that the dysregulation of p68 expression occurs early during tumour development. Finally, we demonstrate that ubiquitylation of p68 occurs in cultured cells, thereby providing a model for the molecular analysis of this process and its potential role in tumorigenesis.

AB - The DEAD box RNA helicase, p68, is upregulated in exponentially growing cells and shows cell cycle-dependent changes in nuclear localization. Although some other DEAD box proteins have been implicated in cancer, there have been no reports of any link between p68 status and carcinogenesis. In the present study we have analysed specimens from 50 patients with colorectal adenocarcinomas, 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 normal tissue. Examination of the levels of p68 mRNA from both normal and tumour tissue showed no obvious specific increase in p68 mRNA levels in tumours nor any evidence of underlying mutations in the p68 coding region. Interestingly, however, the accumulated p68 appears to be poly-ubiquitylated, suggesting a possible defect in proteasome-mediated degradation in these tumours. This overexpression/ubiquitylation is observed in both pre-invasive and invasive lesions suggesting that the dysregulation of p68 expression occurs early during tumour development. Finally, we demonstrate that ubiquitylation of p68 occurs in cultured cells, thereby providing a model for the molecular analysis of this process and its potential role in tumorigenesis.

KW - p68 RNA helicase

KW - Colorectal cancer

KW - Overexpression

KW - Ubiquitylation

M3 - Article

SN - 0950-9232

VL - 20

SP - 7734

EP - 7743

JO - Oncogene

JF - Oncogene

IS - 53

ER -