Document Detail


Making a Short Story Long: Regulation of P-TEFb and HIV-1 Transcriptional Elongation in CD4+ T Lymphocytes and Macrophages.
MedLine Citation:
PMID:  24832049     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
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-CD4+ 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.
Authors:
Rajesh Ramakrishnan; Karen Chiang; Hongbing Liu; Sona Budhiraja; Hart Donahue; Andrew P Rice
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Publication Detail:
Type:  Journal Article     Date:  2012-06-15
Journal Detail:
Title:  Biology     Volume:  1     ISSN:  2079-7737     ISO Abbreviation:  Biology (Basel)     Publication Date:  2012  
Date Detail:
Created Date:  2014-05-16     Completed Date:  2014-05-16     Revised Date:  2014-05-23    
Medline Journal Info:
Nlm Unique ID:  101587988     Medline TA:  Biology (Basel)     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  94-115     Citation Subset:  -    
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