Retroviral replication; tyrosine kinase oncogenes
Our laboratory is interested in the replication of mammalian retroviruses, including the human immunodeficiency virus (HIV) and Moloney murine leukemia virus (M-MuLV). The major approach has been to alter cloned DNA copies of the viral genome by site-directed mutagenesis, and to determine the effects of these mutations on the viral life cycle after transfer of the altered DNAs into cells in culture. These genetic analyses have defined the functional domains of various viral proteins and the sites of their action on viral nucleic acids. We have also expressed reverse transcriptase and integrase in bacteria and studied these enzymes biochemically. We have applied the yeast two-hybrid system to monitor protein-protein interactions between viral proteins, and to identify new host proteins that interact with the Gag, Pol and Env gene products. We are also screening overexpression cDNA libraries, and RNAi knock-down libraries, in mammalian cells to identify novel host proteins involved in retroviral infection.
- Yueh, A., Leung, J., Bhattacharrya, S., Perrone, L.A., de los Santos, K., Pu, S.-y., and Goff, S.P. (2006) Interaction of Moloney murine leukemia virus capsid with Ubc9 and PIASy mediates SUMO-1 addition required early in infection. J. Virol. 80, 342-352.
- Leung, J., Yueh, A., Yuan, B., de los Santos, K., and Goff, S.P. (2006) Interaction of Moloney murine leukemia virus matrix protein with IQGAP. EMBO J. 25, 2155-2166.
- Valente, S.T., and Goff, S.P. (2006) Inhibition of HIV-1 gene expression by a fragment of hnRNP U. Mol. Cell 23, 597-605.
- Cang, Y., Zhang, J., Nicholas, S.A., Bastien, J., Li, B., Zhou, P., and Goff, S.P. (2006) Deletion of DDB1 in mouse brain and lens leads to p53-dependent elimination of proliferating cells. Cell 127, 929-940.
- Naghavi, M.H., Valente, S., Hatziiouannou, T., de los Santos, K., Wen, Y., Mott, C., Gundersen, G.G., and Goff, S.P. (2007) Moesin regulates stable microtubule formation and limits retroviral infection in cultured cells. EMBO J. 26, 41-52.
- Goff, S.P. (2007) Host factors exploited by retroviruses. Nat. Rev. Microbiol. 5, 253-263.
- Wolf, D., and Goff, S.P. (2007) TRIM28 mediates primer binding site-targeted silencing of murine leukemia virus in embryonic cells. Cell 131, 46-57.
- Valente, S.T., Gilmartin, G.M., Mott, C., Falkard, B., and Goff, S.P. (2009) Inhibition of HIV-1 replication by eIF3f. Proc. Natl. Acad. Sci. USA 106, 4071-4078.
- Wolf, D., and Goff, S.P. (2009) Embryonic stem cells use ZFP809 to silence retroviral DNAs. Nature 458, 1201-1204.
- Valente, S.T., Gilmartin, G.M., Venkataraman, K., and Goff, S.P. (2009) HIV-1 mRNA 3' end processing is distinctively regulated by eIF3f, CDK11, and splice factor 9G8. Mol. Cell 36, 279-289.
- Hogg, J.R., and Goff, S.P. (2010) Upf1 senses 3’UTR length to potentiate mRNA decay. Cell, in press.