PMID- 10364329
OWN - NLM
STAT- MEDLINE
DCOM- 19990723
LR  - 20181113
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 73
IP  - 7
DP  - 1999 Jul
TI  - Analysis of the effect of natural sequence variation in Tat and in cyclin T on
      the formation and RNA binding properties of Tat-cyclin T complexes.
PG  - 5777-86
AB  - The biological activity of the human immunodeficiency virus type 1 (HIV-1) Tat
      (Tat1) transcriptional activator requires the recruitment of a Tat1-CyclinT1
      (CycT1) complex to the TAR RNA target encoded within the viral long terminal
      repeat (LTR). While other primate immunodeficiency viruses, such as HIV-2 and
      mandrill simian immunodeficiency virus (SIVmnd), also encode Tat proteins that
      activate transcription via RNA targets, these proteins differ significantly, both
      from each other and from Tat1, in terms of their ability to activate
      transcription directed by LTR promoter elements found in different HIV and SIV
      isolates. Here, we show that CycT1 also serves as an essential cofactor for HIV-2
      Tat (Tat2) and SIVmnd Tat (Tat-M) function. Moreover, the CycT1 complex formed by
      each Tat protein displays a distinct RNA target specificity that accurately
      predicts the level of activation observed with a particular LTR. While Tat2 and
      Tat-M share the ability of Tat1 to bind to CycT1, they differ from Tat1 in that
      they are also able to bind to the related but distinct CycT2. However, the
      resultant Tat-CycT2 complexes fail to bind TAR and are therefore abortive.
      Surprisingly, mutation of a single residue in CycT2 (asparagine 260 to cysteine) 
      rescues the ability of CycT2 to bind Tat1 and also activates not only TAR binding
      by all three Tat-CycT2 complexes but also Tat function. Therefore, the RNA target
      specificity of different Tat-CycT1 complexes is modulated by natural sequence
      variation in both the viral Tat transcriptional activator and in the host cell
      CycT molecule recruited by Tat. Further, the RNA target specificity of the
      resultant Tat-CycT1 complex accurately predicts the ability of that complex to
      activate transcription from a given LTR promoter element.
FAU - Bieniasz, P D
AU  - Bieniasz PD
AD  - Howard Hughes Medical Institute and Department of Genetics, Duke University
      Medical Center, Durham, North Carolina 27710, USA.
FAU - Grdina, T A
AU  - Grdina TA
FAU - Bogerd, H P
AU  - Bogerd HP
FAU - Cullen, B R
AU  - Cullen BR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (CCNT1 protein, human)
RN  - 0 (Ccnt1 protein, mouse)
RN  - 0 (Cyclin T)
RN  - 0 (Cyclins)
RN  - 0 (Gene Products, tat)
RN  - 0 (RNA, Viral)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
SB  - IM
SB  - X
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Cyclin T
MH  - Cyclins/*metabolism
MH  - Gene Products, tat/*metabolism
MH  - *HIV Long Terminal Repeat
MH  - HIV-1/genetics/*metabolism
MH  - HIV-2/genetics/*metabolism
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nucleic Acid Conformation
MH  - RNA, Viral/chemistry/*metabolism
MH  - Simian Immunodeficiency Virus/genetics/*metabolism
MH  - tat Gene Products, Human Immunodeficiency Virus
PMC - PMC112638
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
PST - ppublish
SO  - J Virol. 1999 Jul;73(7):5777-86.