This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Work in our lab involves using adenovirus as a potential oncolytic agent, as well as a tool to study regulation of translation in mammalian cells. The prototype of adenoviral oncolytic therapy is a mutant adenovirus -ONYX-015- which was designed to replicate in tumor cells but not in normal cells. However, in certain tumor cells, 0NYX-015 fails to replicate and this was shown to be because it fails to express the L4 100K protein, which is involved in inhibition of host protein synthesis and specific translation of late viral messages, a process which is critical for a productive adenovirus infection. Therefore, I study the mechanism by which L4-100k is regulated, and how this protein mediates host protein synthesis shutoff. It is a multifunctional protein, has RNA binding activity and is known to bind to the Translation initiation complex and prevent cap-dependent translation of cellular messages, thus promoting virus-specific translation which can occur in a cap-independent manner. This part of the project, which involves TAP purification and Mass spec, aims at identifying novel cellular partners of 100k, which is key to understanding the function of this protein and should give us more insights into how to design more effective oncolytic vectors, and may provide insights into the mechanism of translational control in mammalian cells.
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