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Team:Brown/Project/Ecargo/Background
From 2010.igem.org
E.Cargo
Background
Trans-Activator of Transcription (Tat) is an HIV gene that functions to increase the transcription level of viral genes. The Tat Protein Transduction domain (Tat-PTD) is an 11-amino acid peptide (YGRKKRRQRRR) that allows the protein to traverse cell and nuclear membranes in order to localize to the nucleus.
As a result of years of study, it is now known that there are multiple methods by which this domain operates. Most commonly, the Tat-PTD interacts with heparin sulfate proteogycans (HSPGs) to cause lipid-raft mediated endocytosis. In the endocytosed vesicles, heparinase causes degradation of the heparin sulfate, which releases the bound Tat-PTD (and anything attached to it) into the cytoplasm1. Tat-PTD has also shown the capability to cause nuclear localization of fused proteins3, underscoring its utility in transporting proteins, such as DNA-binding transcription factors, which must localize to chromatin in order to have any effect on the cell.
References
1) Chauhan A, Tikoo A, Kapur AK, Singh M. The taming of the cell penetrating domain of the HIV Tat: myths and realities. J Control Release. 2007;117:148–62.
2) Wadia JS, Dowdy SF. Protein transduction technology. Curr Opin Biotechnol. 2002;13:52–56. doi: 10.1016/S0958-1669(02)00284-7.
3) Yang, Y., Ma, J., Song, Z. and Wu, M., 2002. HIV-1 TAT-mediated protein transduction and subcellular localization using novel expression vectors. FEBS Lett. 532, pp. 36–44.
