Oncoprotein hides tumor

An oncogenic fusion protein hijacks a transcription factor, and uses it to help its tumor avoid immune detection, according to a study by Nabarro and colleagues on page 1399. This is the first description of an oncoprotein that can both transform cells and shut down the immune response.The protein, PAX3-FKHR, results from a reciprocal chromosomal translocation in a rare form of a childhood muscle cancer, alveolar rhabdomyosarcoma (ARMS). Through the combined action of the PAX3 DNA-binding domain and the FKHR transcriptional activation domain, the oncoprotein binds and strongly activates PAX3 target genes such as IGF2. This activity confers rapid and invasive tumor growth.

Now, this group finds that expression of PAX3-FKHR also significantly dampens immune activation, in part by reducing surface levels of class I MHC on transfected cells. A microarray screen revealed...