This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001614-29
Application #
8363764
Study Section
Special Emphasis Panel (ZRG1-BCMB-M (40))
Project Start
2011-06-01
Project End
2012-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
29
Fiscal Year
2011
Total Cost
$50
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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