Sandbox Reserved 654: Difference between revisions
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The histone acetyltransferase portion of PCAF helps with the transactivation of HIV-1 by acetylating Lys28 of Tat. The acetylated Lys28 of Tat interacts with positive elongation factors, which stimulates elongation of nascent HIV-1 transcripts. The bromodomain of PCAF binds with acetylated Lys50 on Tat.[http://www.sciencedirect.com/science/article/pii/S0969212602007542] | The histone acetyltransferase portion of PCAF helps with the transactivation of HIV-1 by acetylating Lys28 of Tat. The acetylated Lys28 of Tat interacts with positive elongation factors, which stimulates elongation of nascent HIV-1 transcripts. The bromodomain of PCAF binds with acetylated Lys50 on Tat.[http://www.sciencedirect.com/science/article/pii/S0969212602007542] | ||
== '''PCAF Bromodomain | == '''PCAF Bromodomain-HIV-1 Tat Interaction and Implications''' == | ||
[[Image:http://ars.els-cdn.com/content/image/1-s2.0-S0969212602007542-gr1.jpg |thumb|250 px|right| Acetylation of the lysine and its effects on chromatin remodeling..]] | [[Image:http://ars.els-cdn.com/content/image/1-s2.0-S0969212602007542-gr1.jpg |thumb|250 px|right| Acetylation of the lysine and its effects on chromatin remodeling..]] | ||
<Structure load='1WUG' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | <Structure load='1WUG' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | ||
== Interaction and Implications == | |||
Protein lysine acetylation is a crucial regulatory mechanism in chromatin remodeling and transcription activation for numerous cellular processes. The human immunodeficiency virus type 1 (HIV-1) trans-activator protein (Tat), for example, stimulates transcription of the HIV genome and promotes viral replication in cells. But Tat transactivation activity is dependent on the acetylation of Lys-50 by p300/CBP. '''Mujtaba 2002'''. When Tat is acetylated at the Lys-50 residue, Tat dissociates from TAR RNA and binds to the PCAF bromodomain instead. This promotes the formation of a multiprotein complex that is responsible for transcription activation of the HIV genome. | |||
== Drug Design == | |||
Current anti-HIV drugs target viral proteins such as reverse transcriptase, protease, and integrase. Garg, R. et al (199) Chem. Rev. 99, 3525. However, the discovery that Tat transactivation requires Lys-50 acetylation for functional transcription of the viral genome reveals a whole new approach to interfering with virus production. Drugs that target viral proteins have proven inadequate in eradicating the virus becuase of the fast rate of mutation in the target proteins leads to developed drug resistance. however, targeting a host cell protein | |||
== '''References''' == | == '''References''' == | ||
<references/> | <references/> | ||
