Expression and functional analysis of human UREB1 in human colorectal carcinoma

Abstract

The protein human upstream regulatory element binding protein 1(hUREB1) is a HECT domain protein whose function is not defined yet. Here, we investigate the function of hUREB1 as a ubiquitin-protein ligase in human colorectal cells. Ectopic expression of the HECT domain of hUREB1 reduces the protein level and transcriptional activity of the p53 tumor suppressor, which is inhibited by the deletion in the HECT domain or point mutations in the essential residues of the HECT domain, implying that the HECT domain of hUREB1 suppresses the transcriptional activity of p53 through a ubiquitin-dependent degradation pathway. Based on the results of Northern blot analysis, RT-PCR and immunohistochemical analyses, the over-expression of hUREB1 is associated with colorectal carcinoma. These findings indicate that hUREB1 can function as a negative regulator of p53 during the colorectal carcinoma progression through the ubiquitination pathway mediated by the HECT domain.