%0 Journal Article
%T Making a Short Story Long: Regulation of P-TEFb and HIV-1 Transcriptional Elongation in CD4+ T Lymphocytes and Macrophages
%A Rajesh Ramakrishnan
%A Karen Chiang
%A Hongbing Liu
%A Sona Budhiraja
%A Hart Donahue
%A Andrew P. Rice
%J Biology
%D 2012
%I MDPI AG
%R 10.3390/biology1010094
%X Productive transcription of the integrated HIV-1 provirus is restricted by cellular factors that inhibit RNA polymerase II elongation. The viral Tat protein overcomes this by recruiting a general elongation factor, P-TEFb, to the TAR RNA element that forms at the 5¡¯ end of nascent viral transcripts. P-TEFb exists in multiple complexes in cells, and its core consists of a kinase, Cdk9, and a regulatory subunit, either Cyclin T1 or Cyclin T2. Tat binds directly to Cyclin T1 and thereby targets the Cyclin T1/P-TEFb complex that phosphorylates the CTD of RNA polymerase II and the negative factors that inhibit elongation, resulting in efficient transcriptional elongation. P-TEFb is tightly regulated in cells infected by HIV-1¡ªCD4 + T lymphocytes and monocytes/macrophages. A number of mechanisms have been identified that inhibit P-TEFb in resting CD4 + T lymphocytes and monocytes, including miRNAs that repress Cyclin T1 protein expression and dephosphorylation of residue Thr186 in the Cdk9 T-loop. These repressive mechanisms are overcome upon T cell activation and macrophage differentiation when the permissivity for HIV-1 replication is greatly increased. This review will summarize what is currently known about mechanisms that regulate P-TEFb and how this regulation impacts HIV-1 replication and latency.
%K P-TEFb
%K HIV-1
%K Tat
%K T-loop phosphorylation
%K Cyclin T1
%K miRNA
%U http://www.mdpi.com/2079-7737/1/1/94