Polyomavirus middle-T antigen lacking a membrane anchor sequence accumulates in the nucleus.

Three proteins expressed early in the replicative cycle of polyomavirus also play an essential role during virus-mediated tumorigenesis. One of the proteins, middle-T antigen, has been shown to bind cellular proteins involved in cell signalling such as c-Src, phosphatase 2A, phosphatidylinositol 3-kinase and SHC. Association of middle-T antigen with cellular membranes has been shown to be essential for middle-T-mediated cell transformation.

v-erbA overexpression is required to extinguish c-erbA function in erythroid cell differentiation and regulation of the erbA target gene CAII.

The v-erbA oncoprotein represents a retrovirus-transduced oncogenic version of the thyroid hormone (T3/T4) receptor c-erbA (type alpha). It contributes to virus-induced erythroleukemia by efficiently arresting differentiation of red cell progenitors and by suppressing transcription of erythrocyte-specific genes. Here, we show that v-erbA and c-erbA bind directly to sequences within the promoter of the erythrocyte-specific carbonic anhydrase II (CAII), a gene whose transcription is efficiently suppressed by v-erbA.

Temperature-sensitive v-sea transformed erythroblasts: a model system to study gene expression during erythroid differentiation.

The isolation and characterization of a temperature-sensitive mutant (ts1 S13) of the avian erythroblastosis virus, S13, is described. The temperature-sensitive lesion in ts1 S13 was identified as affecting the tyrosine kinase activity but not the plasma membrane localization of the ts1 S13 v-sea gene product. Erythroblasts transformed by ts1 S13 can be induced to synchronously differentiate into erythrocytes in an erythropoietin (EPO)-dependent fashion.

v-erbA specifically suppresses transcription of the avian erythrocyte anion transporter (band 3) gene.

Previous work has established that the v-erbA oncogene inhibits the temperature-induced differentiation of chick erythroblasts transformed with temperature-sensitive oncogene mutants. Here we demonstrate that v-erbA in differentiating erythroblasts specifically arrests expression of the erythrocyte anion transporter (band 3) gene at the transcriptional level. The v-erbA-induced differentiation block can be overcome by inducing cells to differentiate at alkaline pH.