Expression analysis of the gene encoding for the U-box-type ubiquitin ligase UBE4A in human tissues

The Ubiquitination Factor E4A gene (UBE4A) encodes for a U-box-type ubiquitin ligase, originally described as an E4 ubiquitination factor. UBE4A is a mammalian homolog of Saccharomyces cerevisiae Ufd2. The UBE4A gene has been mapped on the human chromosome region 11q23.3, a critical region involved in some specific cancers such as neuroblastoma. Northern blots analysis on foetal and adult human tissues revealed a single band of approximately 7.5 kb transcript most abundant in the heart, skeletal muscle and kidney. We generated a polyclonal antibody to UBE4A and performed immunoblot and immunohistochemical analysis. The UBE4A protein appeared as a single band of approximately 125 kDa. UBE4A was present in the skeletal muscle, kidney and liver; a faint band was visible in peripheral blood leukocytes and spleen. We did not reveal expression of UBE4A in whole brain, colon, lung and heart. At the cellular level, UBE4A results predominantly expressed in the nucleus and the cytoplasm of cortical neurons and liver and in the nucleus of tubular kidney cells. In the liver, the nucleus of similar cells appeared to be unstained or stained at different levels suggesting that UBE4A may have a cell cycle dependent expression or a role of in cell cycle control. In conclusion, our results show that UBE4A is expressed in different tissues in a pattern that seems to be dependent from cell type and cell cycle and that UBE4A might have a specific role in different biochemical processes other than ubiquitination, including growth or differentiation.